MCL1 encodes a short-lived BCL2-family survival factor best known as the mitochondrial outer-membrane protein Mcl-1L, whose BH3-binding groove sequesters BAK, BAX, and BH3-only proteins to restrain mitochondrial outer membrane permeabilization, cytochrome-c release, and downstream caspase activation. Alternative splicing produces the short MCL-1S isoform, and caspase cleavage can also generate pro-apoptotic MCL1 fragments, separating conditional pro-death proteoforms from the canonical anti-apoptotic long isoform. MCL1 abundance is controlled rapidly by phosphorylation, ubiquitination, and deubiquitination, and contextual MCL1 pools have been linked to autophagy control, anoikis resistance, DNA-damage responses, and mitochondrial dynamics.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001709 cell fate determination | NAS PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | MODIFY | Summary: The short MCL-1S splice product promotes apoptosis, but cell fate determination is too broad. Reason: PMID:10837489 identifies a pro-apoptotic splice product; the supported biology is regulation of apoptosis by an MCL1 isoform rather than generic cell fate determination. Proposed replacements: positive regulation of apoptotic process |
| GO:0001836 release of cytochrome c from mitochondria | IBA GO_REF:0000033 | MODIFY | Summary: Canonical MCL-1L restrains cytochrome-c release rather than forming a release pore. Reason: The inherited family term conflates pro-survival and pore-forming BCL2 relatives. For canonical MCL1, the specific supported role is inhibition of BAX/BAK-dependent cytochrome-c release. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: REGULATORY SIGN INVERSION Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS SOURCE BUT NOT TARGET The BCL2 family includes proapoptotic cytochrome-c release effectors, but MCL1 is a pro-survival antagonist at this step. Proposed replacements: negative regulation of release of cytochrome c from mitochondria |
| GO:0005515 protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:16697956 Mitochondria primed by death signals determine cellular addi... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:17097560 Mechanisms of apoptosis sensitivity and resistance to the BH... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:17428862 Induction of apoptosis by the severe acute respiratory syndr... | REMOVE | Summary: The SARS-CoV 7a co-IP row is only a viral generic PPI for MCL1. Reason: The interaction may be real, but GO:0005515 does not add an informative MCL1 molecular function and no better MCL1 activity term is exposed for this viral contact. |
| GO:0005515 protein binding | IPI PMID:17525735 ERK1/2-dependent phosphorylation of BimEL promotes its rapid... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:17525735 ERK1/2-dependent phosphorylation of BimEL promotes its rapid... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:18040043 Small molecule obatoclax (GX15-070) antagonizes MCL-1 and ov... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:18981409 Apoptosis is triggered when prosurvival Bcl-2 proteins canno... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:19074266 Mechanism of apoptosis induction by inhibition of the anti-a... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:19605477 The hepatitis C virus core protein contains a BH3 domain tha... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:19968986 Mcl-1(128-350) fragment induces apoptosis through direct int... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:19968986 Mcl-1(128-350) fragment induces apoptosis through direct int... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:20023629 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cel... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:20023629 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cel... | REMOVE | Summary: This is a substrate or stabilizer contact rather than a specific MCL1 molecular function. Reason: HUWE1/USP9X and Caveolin-family papers regulate MCL1 stability; a reciprocal MCL1 annotation to generic protein binding would add a low-information contact instead of MCL1 apoptotic activity. |
| GO:0005515 protein binding | IPI PMID:20023629 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cel... | REMOVE | Summary: This is a substrate or stabilizer contact rather than a specific MCL1 molecular function. Reason: HUWE1/USP9X and Caveolin-family papers regulate MCL1 stability; a reciprocal MCL1 annotation to generic protein binding would add a low-information contact instead of MCL1 apoptotic activity. |
| GO:0005515 protein binding | IPI PMID:20085765 Noxa is necessary for hydrogen peroxide-induced caspase-depe... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:20085765 Noxa is necessary for hydrogen peroxide-induced caspase-depe... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21139567 MCL-1 is a stress sensor that regulates autophagy in a devel... | UNDECIDED | Summary: MCL1-BECN1 binding is plausible in autophagy regulation, but the cached paper does not resolve this row. Reason: The abstract-only stress-sensor source does not expose enough of the BECN1 interaction assay to choose a specific MCL1 molecular function. |
| GO:0005515 protein binding | IPI PMID:21199865 Mutation to Bax beyond the BH3 domain disrupts interactions ... | UNDECIDED | Summary: The cached abstract does not expose the exact MCL1/BIM assertion from this BAX structural paper. Reason: The paper may contain the curated experiment, but the cache is abstract-only and is insufficient to adjudicate the BIM row. |
| GO:0005515 protein binding | IPI PMID:21199865 Mutation to Bax beyond the BH3 domain disrupts interactions ... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21454712 Noxa/Bcl-2 protein interactions contribute to bortezomib res... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21458670 Bcl-x(L) retrotranslocates Bax from the mitochondria into th... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:21507240 Role of bile salt in regulating Mcl-1 phosphorylation and ch... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:21507240 Role of bile salt in regulating Mcl-1 phosphorylation and ch... | REMOVE | Summary: This stability-scaffolding contact is not an informative MCL1 molecular-function assertion. Reason: The partner regulates MCL1 abundance or stability; a reciprocal MCL1 annotation to generic protein binding obscures the anti-apoptotic BH3-groove function. |
| GO:0005515 protein binding | IPI PMID:22277751 Caveolin-1 regulates Mcl-1 stability and anoikis in lung car... | REMOVE | Summary: This stability-scaffolding contact is not an informative MCL1 molecular-function assertion. Reason: The partner regulates MCL1 abundance or stability; a reciprocal MCL1 annotation to generic protein binding obscures the anti-apoptotic BH3-groove function. |
| GO:0005515 protein binding | IPI PMID:22277751 Caveolin-1 regulates Mcl-1 stability and anoikis in lung car... | REMOVE | Summary: This stability-scaffolding contact is not an informative MCL1 molecular-function assertion. Reason: The partner regulates MCL1 abundance or stability; a reciprocal MCL1 annotation to generic protein binding obscures the anti-apoptotic BH3-groove function. |
| GO:0005515 protein binding | IPI PMID:22516262 Chemical genomics identifies small-molecule MCL1 repressors ... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:22516262 Chemical genomics identifies small-molecule MCL1 repressors ... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:22516262 Chemical genomics identifies small-molecule MCL1 repressors ... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:23055042 Human Bop is a novel BH3-only member of the Bcl-2 protein fa... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:23245996 Synthetic lethal interaction of combined BCL-XL and MEK inhi... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:23680104 The novel BH3 α-helix mimetic JY-1-106 induces apoptosis in ... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:24113155 Placental autophagy regulation by the BOK-MCL1 rheostat. | REMOVE | Summary: BECN1 explains the autophagy process row but should not be retained as generic MCL1 protein binding. Reason: The BOK/MCL1 rheostat evidence is kept as negative regulation of autophagy; GO:0005515 itself adds no precise molecular function for MCL1. |
| GO:0005515 protein binding | IPI PMID:26431330 Subcellular localization of PUMA regulates its pro-apoptotic... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:26431330 Subcellular localization of PUMA regulates its pro-apoptotic... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:26859456 Exploitation of the Apoptosis-Primed State of MYCN-Amplified... | MODIFY | Summary: MCL1 binds a BH3-containing BCL2-family or BH3-like ligand rather than performing undifferentiated protein binding. Reason: The source supports binding through the pro-survival MCL1 groove to a BH3 ligand or BAX/BAK BH3 helix; GO:0051434 captures that function more precisely than GO:0005515. Proposed replacements: BH3 domain binding |
| GO:0005515 protein binding | IPI PMID:27013495 The deubiquitinase Usp27x stabilizes the BH3-only protein Bi... | UNDECIDED | Summary: The exact partner-specific MCL1 interaction is hidden behind an abstract-only cache. Reason: Do not reject an experimental IPI row from incomplete evidence, but do not force it to BH3 domain binding until the partner table or full assay is available. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The row comes from a large-scale binary-interactome screen and adds only generic protein binding. Reason: MCL1 already has curated BCL2-family binding evidence from focused apoptosis papers; this high-throughput generic interaction is not an informative molecular-function annotation. |
| GO:0005634 nucleus | IDA PMID:20467439 ATM-dependent expression of IEX-1 controls nuclear accumulat... | KEEP AS NON CORE | Summary: A nuclear/nucleoplasmic MCL1 pool has been reported in DNA-damage contexts. Reason: MCL1 is primarily mitochondrial, but the ATM/IEX-1 source and UniProt-derived propagation make a contextual nuclear localization plausible rather than a core OMM localization. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A nuclear/nucleoplasmic MCL1 pool has been reported in DNA-damage contexts. Reason: MCL1 is primarily mitochondrial, but the ATM/IEX-1 source and UniProt-derived propagation make a contextual nuclear localization plausible rather than a core OMM localization. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A nuclear/nucleoplasmic MCL1 pool has been reported in DNA-damage contexts. Reason: MCL1 is primarily mitochondrial, but the ATM/IEX-1 source and UniProt-derived propagation make a contextual nuclear localization plausible rather than a core OMM localization. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: A non-mitochondrial cytoplasmic MCL1 pool is plausible but secondary to the OMM pool. Reason: MCL1 is primarily a membrane-associated mitochondrial survival factor; cytoplasm is broad contextual localization rather than the core site of action. |
| GO:0005737 cytoplasm | TAS PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | KEEP AS NON CORE | Summary: A non-mitochondrial cytoplasmic MCL1 pool is plausible but secondary to the OMM pool. Reason: MCL1 is primarily a membrane-associated mitochondrial survival factor; cytoplasm is broad contextual localization rather than the core site of action. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0005739 mitochondrion | IDA PMID:7896880 The intracellular distribution and pattern of expression of ... | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0005741 mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The mitochondrial outer membrane is the core site where MCL1 restrains BAK/BAX-dependent MOMP. Reason: MCL1 constitutively engages BAK at the mitochondrial outer membrane and its C-terminal transmembrane region anchors the protein at apoptotic membranes. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS TRANSFER The ancestral BCL2-family mitochondrial outer-membrane assertion is valid for MCL1. |
| GO:0005741 mitochondrial outer membrane | TAS PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | ACCEPT | Summary: The mitochondrial outer membrane is the core site where MCL1 restrains BAK/BAX-dependent MOMP. Reason: MCL1 constitutively engages BAK at the mitochondrial outer membrane and its C-terminal transmembrane region anchors the protein at apoptotic membranes. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS TRANSFER The ancestral BCL2-family mitochondrial outer-membrane assertion is valid for MCL1. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | MODIFY | Summary: Cytosol is less precise than cytoplasmic membrane association for MCL1. Reason: MCL1 is cytoplasmic in the broad sense but the anti-apoptotic long isoform is membrane-associated rather than a soluble cytosolic enzyme. Proposed replacements: cytoplasm |
| GO:0005829 cytosol | ISS GO_REF:0000024 | MODIFY | Summary: Cytosol is less precise than cytoplasmic membrane association for MCL1. Reason: MCL1 is cytoplasmic in the broad sense but the anti-apoptotic long isoform is membrane-associated rather than a soluble cytosolic enzyme. Proposed replacements: cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6790041 | MODIFY | Summary: Cytosol from a Reactome module on induction of MCL1 expression; MCL1 is membrane-anchored, and the term is redirected to cytoplasm like the other rows for this term. Reason: The other rows for this term in the review are redirected to cytoplasm, because MCL1 is a membrane-anchored protein of the mitochondrial outer membrane and other intracellular membranes rather than a soluble cytosolic protein, while a cytoplasmic location is correct. This Reactome row makes the same claim; it derives from a pathway module on induction of MCL1 expression rather than from a localization experiment, which limits its evidence but does not change the claim. Rows that share a term are judged alike, so it is redirected to cytoplasm with the others rather than removed. Proposed replacements: cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9851112 | MODIFY | Summary: Cytosol from a Reactome module on induction of MCL1 expression; MCL1 is membrane-anchored, and the term is redirected to cytoplasm like the other rows for this term. Reason: The other rows for this term in the review are redirected to cytoplasm, because MCL1 is a membrane-anchored protein of the mitochondrial outer membrane and other intracellular membranes rather than a soluble cytosolic protein, while a cytoplasmic location is correct. This Reactome row makes the same claim; it derives from a pathway module on induction of MCL1 expression rather than from a localization experiment, which limits its evidence but does not change the claim. Rows that share a term are judged alike, so it is redirected to cytoplasm with the others rather than removed. Proposed replacements: cytoplasm |
| GO:0006974 DNA damage response | IMP PMID:20467439 ATM-dependent expression of IEX-1 controls nuclear accumulat... | KEEP AS NON CORE | Summary: ATM-dependent nuclear MCL1 contributes to the DNA-damage response in the IEX-1 pathway. Reason: The cached full text supports nuclear MCL1 as a DNA-damage-context activity, secondary to its canonical mitochondrial apoptosis function. |
| GO:0008053 mitochondrial fusion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: MCL1 has a curated peripheral role in mitochondrial dynamics. Reason: This is not the core outer-membrane BH3-groove activity, but PAINT treats the mitochondrial-fusion assertion as curated BCL2-family mitochondrial-dynamics biology and there is no target-specific loss evidence. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000883418 · PTN000883418 SUPPORTS TRANSFER The mitochondrial-dynamics assertion is retained as contextual rather than central MCL1 apoptosis function. |
| GO:0008320 transmembrane protein transporter activity | TAS PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | REMOVE | Summary: MCL1 is a transmembrane regulator, not a transmembrane protein transporter. Reason: The MCL-1S splice study does not expose transporter chemistry; the anti-apoptotic activity is BH3-groove binding to apoptotic regulators. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IBA GO_REF:0000033 | MODIFY | Summary: MCL1 restrains the intrinsic pathway downstream of DNA damage but is not DNA-damage-specific machinery. Reason: The inherited term is trigger-specific; the more precise MCL1 activity is negative regulation of BAX/BAK-mediated MOMP within intrinsic apoptotic signaling. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: REGULATORY SIGN INVERSION GRANULARITY MISMATCH Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS SOURCE BUT NOT TARGET The family supports intrinsic-apoptosis control, but MCL1 is a negative MOMP regulator rather than DNA-damage-specific positive signaling machinery. |
| GO:0010507 negative regulation of autophagy | IMP PMID:24113155 Placental autophagy regulation by the BOK-MCL1 rheostat. | KEEP AS NON CORE | Summary: MCL1 can repress autophagy through BECN1 in trophoblast cells. Reason: The BOK-MCL1 rheostat evidence supports inhibition of BECN1-dependent autophagy, but this is contextual relative to the core MOMP-survival role. |
| GO:0012501 programmed cell death | IEA GO_REF:0000117 | MODIFY | Summary: Programmed cell death is a true but unnecessarily broad consequence of MCL1 apoptosis regulation. Reason: The ARBA row should be tightened to MCL1's anti-apoptotic mitochondrial role rather than retained as a top-level programmed-cell-death assertion. |
| GO:0015267 channel activity | IBA GO_REF:0000033 | REMOVE | Summary: MCL1 is not known to be a direct apoptotic membrane channel. Reason: The channel-capacity PAINT term is supported by BAX, BAK, and BCL2-family evidence but is unsafe for MCL1, whose OMM work is sequestration of pore-forming BAK/BAX. Propagation Review Root cause: PROPAGATION BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS SOURCE BUT NOT TARGET Channel activity is biologically supported for BAX/BAK/BCL2 donors but should not be projected to the anti-apoptotic MCL1 subfamily. |
| GO:0016020 membrane | IDA PMID:7896880 The intracellular distribution and pattern of expression of ... | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: This broad localization is compatible with membrane-associated mitochondrial MCL1. Reason: MCL1 is a single-pass membrane protein with prominent mitochondrial localization; this term is broad but biologically consistent with the more precise outer-membrane role. |
| GO:0019725 cellular homeostasis | NAS PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | MARK AS OVER ANNOTATED | Summary: Cellular homeostasis is too vague for the MCL-1S splice-product paper. Reason: The cited abstract supports apoptosis regulation by alternative MCL1 isoforms; cellular homeostasis overgeneralizes that finding. |
| GO:0034097 response to cytokine | IDA PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by ... | MARK AS OVER ANNOTATED | Summary: IL-10 changes MCL1 expression in activated B cells (PMID:9184696); an expression response rather than a role of MCL1 in the response to cytokine. Reason: The cited study relates the effects of IL-10 on apoptosis and proliferation of activated B cells to changes in the expression of MCL1 and related proteins, so the row records a real expression response, and the annotation already carries the acts_upstream_of_or_within qualifier. A change in MCL1 expression after cytokine treatment shows that MCL1 is regulated by the cytokine, not that it takes part in the response as an actor. The term over-reads an expression result and is marked as an over-annotation rather than removed. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | MODIFY | Summary: MCL1 is a direct negative regulator of the mitochondrial branch of apoptotic signaling. Reason: The InterPro-derived parent term is directionless and should be tightened to MCL1 inhibition of MOMP. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce... | MODIFY | Summary: This source supports MCL1 survival activity; the positive-apoptosis sign is wrong for long MCL1. Reason: The NSCLC source describes MCL1 dependence and BIM sequestration, so the MCL1 product is restraining rather than promoting apoptosis in that assay. |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: MCL1 inhibits apoptosis by restraining BAX/BAK-driven mitochondrial permeabilization. Reason: The broad negative-regulation row is correct but should be made specific to mitochondrial outer membrane permeabilization. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS TRANSFER The PAINT node and direct MCL1 evidence support inherited anti-apoptotic BCL2-family function. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:20041405 Effects of microRNA-29 on apoptosis, tumorigenicity, and pro... | MODIFY | Summary: MCL1 inhibits apoptosis by restraining BAX/BAK-driven mitochondrial permeabilization. Reason: The broad negative-regulation row is correct but should be made specific to mitochondrial outer membrane permeabilization. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | MODIFY | Summary: MCL1 inhibits apoptosis by restraining BAX/BAK-driven mitochondrial permeabilization. Reason: The broad negative-regulation row is correct but should be made specific to mitochondrial outer membrane permeabilization. |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: The neuron-specific positive-regulation term has the wrong sign for MCL1 survival biology. Reason: Available MCL1 neuron/oxidative-stress evidence points to MCL1 stabilization protecting neurons, so the positive apoptotic process term should be inverted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: REGULATORY SIGN INVERSION Sources checked: PANTHER:PTN002600668 · PTN002600668 SUPPORTS SOURCE BUT NOT TARGET The propagated child term captures the neuronal oxidative-stress context but not MCL1's inhibitory sign. Proposed replacements: negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| GO:0046982 protein heterodimerization activity | IPI PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | UNDECIDED | Summary: The MCL-1S paper does not expose enough full-text detail for this specific heterodimerization row. Reason: The abstract establishes MCL-1S/MCL-1L heterodimerization, but these GOA rows name TP53 and BAK1; keep unresolved until the full interaction panel can be checked. |
| GO:0046982 protein heterodimerization activity | IPI PMID:10837489 MCL-1S, a splicing variant of the antiapoptotic BCL-2 family... | UNDECIDED | Summary: The MCL-1S paper does not expose enough full-text detail for this specific heterodimerization row. Reason: The abstract establishes MCL-1S/MCL-1L heterodimerization, but these GOA rows name TP53 and BAK1; keep unresolved until the full interaction panel can be checked. |
| GO:0051400 BH domain binding | IEA GO_REF:0000117 | MODIFY | Summary: The informative MCL1 binding activity is recognition of BH3 helices. Reason: A broad BH-domain-binding row is directionally close but less precise than the BH3-domain binding term used for BCL2-family pro-survival grooves. Proposed replacements: BH3 domain binding |
| GO:0051434 BH3 domain binding | IEA GO_REF:0000107 | ACCEPT | Summary: BH3-domain binding is the core molecular function of pro-survival MCL1. Reason: MCL1 recognizes BH3 helices from BAK and BH3-only proteins through its pro-survival binding groove. |
| GO:0051434 BH3 domain binding | IPI PMID:21036904 Heterodimerization of BAK and MCL-1 activated by detergent m... | ACCEPT | Summary: BH3-domain binding is the core molecular function of pro-survival MCL1. Reason: MCL1 recognizes BH3 helices from BAK and BH3-only proteins through its pro-survival binding groove. |
| GO:0051434 BH3 domain binding | IPI PMID:21036904 Heterodimerization of BAK and MCL-1 activated by detergent m... | ACCEPT | Summary: BH3-domain binding is the core molecular function of pro-survival MCL1. Reason: MCL1 recognizes BH3 helices from BAK and BH3-only proteins through its pro-survival binding groove. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000108 | REMOVE | Summary: The transmembrane-transport row is an unsafe logical consequence of the inherited channel annotation. Reason: Because direct MCL1 channel activity is not supported, the downstream logical transmembrane-transport inference should also be removed. |
| GO:0071806 protein transmembrane transport | IEA GO_REF:0000108 | REMOVE | Summary: The protein-transport row is an unsafe logical consequence of the transporter annotation. Reason: MCL1 is a membrane-anchored apoptosis regulator, not a protein transmembrane transporter. |
| GO:0097136 Bcl-2 family protein complex | IDA PMID:21199865 Mutation to Bax beyond the BH3 domain disrupts interactions ... | ACCEPT | Summary: MCL1 forms BCL2-family complexes with BAK, BAX, and BH3-only proteins. Reason: The row captures the pro-survival MCL1 groove bound to BCL2-family partners in complexes that tune MOMP. |
| GO:0097136 Bcl-2 family protein complex | IEA GO_REF:0000117 | ACCEPT | Summary: MCL1 forms BCL2-family complexes with BAK, BAX, and BH3-only proteins. Reason: The row captures the pro-survival MCL1 groove bound to BCL2-family partners in complexes that tune MOMP. |
| GO:0097136 Bcl-2 family protein complex | IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce... | ACCEPT | Summary: MCL1 forms BCL2-family complexes with BAK, BAX, and BH3-only proteins. Reason: The row captures the pro-survival MCL1 groove bound to BCL2-family partners in complexes that tune MOMP. |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IBA GO_REF:0000033 | MODIFY | Summary: MCL1 prevents apoptotic signaling after cytokine withdrawal. Reason: Cytokine withdrawal decreases MCL1 stability and licenses mitochondrial apoptosis; MCL1 therefore negatively regulates this ligand-withdrawal route. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000135648 · PTN000135648 SUPPORTS TRANSFER The PAINT cytokine-withdrawal row is grounded in MCL1 itself and only needs the inhibitory role made explicit. Proposed replacements: negative regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IEA GO_REF:0000107 | MODIFY | Summary: MCL1 prevents apoptotic signaling after cytokine withdrawal. Reason: Cytokine withdrawal decreases MCL1 stability and licenses mitochondrial apoptosis; MCL1 therefore negatively regulates this ligand-withdrawal route. Proposed replacements: negative regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand | IMP PMID:16543145 Glycogen synthase kinase-3 regulates mitochondrial outer mem... | MODIFY | Summary: MCL1 prevents apoptotic signaling after cytokine withdrawal. Reason: Cytokine withdrawal decreases MCL1 stability and licenses mitochondrial apoptosis; MCL1 therefore negatively regulates this ligand-withdrawal route. Proposed replacements: negative regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| GO:1902531 regulation of intracellular signal transduction | IEA GO_REF:0000117 | TOO GENERAL | Summary: Generic regulation of intracellular signal transduction from an ARBA rule; entailed by the specific apoptotic signalling annotations of this review. Reason: Regulation of intracellular signal transduction is entailed by the more specific annotations of this review that place MCL1 in the negative regulation of intrinsic apoptotic signalling, so the machine-generated term is true of MCL1 but adds nothing to them. A true but less informative term is recorded as too general rather than removed. |
| GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: MCL1 stabilization protects neurons from oxidative-stress apoptosis rather than promoting that pathway. Reason: The source context around FBW7beta/Parkin points to MCL1 as the stabilized pro-survival effector; invert the sign to negative regulation. Proposed replacements: negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IGI PMID:23858059 Parkin-dependent degradation of the F-box protein Fbw7β prom... | MODIFY | Summary: MCL1 stabilization protects neurons from oxidative-stress apoptosis rather than promoting that pathway. Reason: The source context around FBW7beta/Parkin points to MCL1 as the stabilized pro-survival effector; invert the sign to negative regulation. Proposed replacements: negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| GO:2000811 negative regulation of anoikis | IMP PMID:22277751 Caveolin-1 regulates Mcl-1 stability and anoikis in lung car... | KEEP AS NON CORE | Summary: MCL1 can suppress detachment-induced apoptosis in cancer-cell anoikis assays. Reason: The Cav1/MCL1 paper supports anoikis resistance through MCL1 stabilization, but this is a cancer detachment context layered over the core BCL2-family survival activity. |
| GO:2001233 regulation of apoptotic signaling pathway | IEA GO_REF:0000117 | MODIFY | Summary: MCL1 directly restrains the mitochondrial apoptotic signaling checkpoint. Reason: The ARBA parent term can be tightened to negative regulation of MOMP in apoptotic signaling. |
| GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | IMP PMID:20921992 Prevention of cytokine withdrawal-induced apoptosis by Mcl-1... | KEEP AS NON CORE | Summary: MCL1 prevents cytokine-withdrawal apoptosis through BIM-dependent mitochondrial control. Reason: The term is correct for the IL-3 withdrawal source, but it is a growth-factor-withdrawal specialization of the same MOMP checkpoint rather than a separate core activity. |
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Download this section (compressed HTML)Q: Should GOA represent the pro-apoptotic MCL-1S isoform with isoform-specific positive-apoptosis annotations rather than mixing MCL-1S biology into the canonical MCL1 record?
Q: Should MCL1-specific matrix and mitochondrial-fusion functions be separated from outer-membrane BCL2-family MOMP control in future GO annotations?
Experiment: For proposed MCL1 interactions outside BAK/BAX/BH3-only ligands, map the interface, test whether the partner changes BAK/BAX sequestration or MCL1 turnover, and measure MOMP separately from terminal viability or caspase readouts.
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