SKN-1 is the C. elegans ortholog of mammalian Nrf1/Nrf2 (CNC/bZIP) transcription factors, functioning as the master regulator of oxidative stress responses and xenobiotic detoxification. SKN-1 has three major isoforms with distinct functions: SKN-1A is ER-associated and mediates proteasome stress responses; SKN-1B localizes to ASI chemosensory neurons and mediates dietary restriction effects on longevity; SKN-1C is the primary intestinal isoform regulating Phase II detoxification genes. SKN-1 binds DNA as a monomer using a unique mechanism combining a bZIP-like basic region with an N-terminal arm for minor groove contacts. Key target genes include glutathione S-transferases (gst-4, gst-1), glutamate-cysteine ligase (gcs-1), and proteasome subunits. SKN-1 is regulated by p38/PMK-1 phosphorylation (activation), WDR-23/CUL4/DDB1 ubiquitin ligase complex (degradation), and insulin/IGF-1 signaling via AKT kinases (inhibition). Beyond stress responses, SKN-1 plays an essential developmental role in mesendoderm specification during embryogenesis, specifying the fate of ventral blastomeres that give rise to the pharynx and intestine. Maternal SKN-1 protein is nuclear and accumulates to higher levels in the P1 blastomere and its descendants than in AB. In larvae and adults SKN-1 is present in ASI neuron nuclei under normal conditions and accumulates in intestinal nuclei in response to oxidative stress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: SKN-1 binds DNA through a unique mechanism involving a bZIP-like basic region combined with an N-terminal arm that contacts the minor groove. Canonical Phase II response element binding is well-established. Reason: IBA annotation supported by phylogenetic inference from mammalian Nrf2 orthologs. Crystal structure (PMID:9628487) and extensive biochemical studies demonstrate SKN-1 sequence-specific DNA binding to cis-regulatory regions via its basic region and N-terminal arm. Supporting Evidence: PMID:12869585 SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively PMID:9628487 A new DNA-binding motif in the Skn-1 binding domain-DNA complex file:worm/skn-1/skn-1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: SKN-1 is a well-characterized transcription factor that activates Phase II detoxification genes and developmental target genes through specific binding to promoter regions and recruitment of RNA Pol II machinery. Reason: IBA annotation reflects conserved transcription factor function. SKN-1 directly activates transcription of gcs-1, gst-4, and other target genes in response to oxidative stress (PMID:16166371, PMID:12869585). Core molecular function of this transcription factor. Supporting Evidence: PMID:12869585 During postembryonic stages, SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively PMID:16166371 In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei, where SKN-1 activates transcription of gcs-1, a phase II detoxification enzyme gene |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: SKN-1 translocates to the nucleus upon oxidative stress to activate target gene transcription. Nuclear localization is dynamically regulated by p38/PMK-1 phosphorylation. Reason: Core cellular component annotation. Nuclear localization is dynamically regulated and essential for SKN-1 transcriptional activity. Basally present in ASI neuron nuclei, stress-inducible in intestinal nuclei. Supporting Evidence: PMID:12869585 SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress PMID:16166371 PMK-1 p38 MAPK pathway regulates the oxidative stress response via the CNC transcription factor SKN-1 |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: SKN-1 regulates transcription of multiple target genes through RNA polymerase II, including Phase II detoxification genes and developmental markers. Reason: IBA annotation supported by extensive experimental evidence. SKN-1 is a master transcriptional regulator of stress response and developmental programs. Binding to promoters directly activates target gene expression. Supporting Evidence: PMID:16166371 SKN-1 activates transcription of gcs-1, a phase II detoxification enzyme gene PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation based on InterPro domain mapping for NFE2-like domain (IPR047167), which characterizes bZIP-like transcription factors. Reason: InterPro-based annotation is accurate given SKN-1's characterized DNA-binding domain and experimental validation of sequence-specific binding through crystal structure analysis. Supporting Evidence: PMID:9628487 A new DNA-binding motif in the Skn-1 binding domain-DNA complex. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: General DNA binding annotation based on combined automated methods. Reason: Accurate but general annotation. More specific DNA-binding terms are also annotated. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro bZIP domain mappings. Reason: Accurate annotation consistent with SKN-1's established function as a transcription factor. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location mapping. Reason: Duplicates the IBA and IDA annotations but provides additional automated evidence support. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: SKN-1 localizes to cytoplasm under basal conditions and translocates to nucleus upon stress activation. Reason: Accurate annotation. Cytoplasmic localization under non-stress conditions is well-documented. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: SKN-1 isoform A has been shown to localize to mitochondria. Reason: Mitochondrial localization is specific to SKN-1A isoform and has been experimentally validated (PMID:23040073). |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000043 | ACCEPT | Summary: General transcription annotation from UniProt keyword mapping. Reason: Accurate but general. More specific transcription regulatory terms are also present. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro domain mapping. Reason: Accurate annotation. SKN-1 regulates transcription of stress response and developmental genes. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro NFE2-like domain. Reason: Accurate annotation consistent with SKN-1's established function in RNA polymerase II-dependent transcription. |
| GO:0006417 regulation of translation | IEA GO_REF:0000043 | REMOVE | Summary: IEA annotation from UniProt keyword mapping. Evidence for SKN-1 directly regulating translation is limited. Reason: This IEA annotation (from UniProt keyword KW-0810) is an over-annotation and should be removed. SKN-1 is a bZIP/CNC-family transcription factor that lacks any recognized RNA-binding or translation-factor domain, and its only established regulatory activity is transcriptional (RNA polymerase II target genes). An OpenScientist run testing this annotation found that the keyword most likely conflates SKN-1 being activated by translation inhibition (acting as a downstream transcriptional effector) with SKN-1 directly regulating translation; no experimental evidence supports a direct translational role. Supporting Evidence: file:worm/skn-1/skn-1-hypotheses/translation-regulation-overannotation/openscientist.md the protein lacks all recognized RNA-binding and translation-factor domains. file:worm/skn-1/skn-1-hypotheses/translation-regulation-overannotation/openscientist.md The curation recommendation is to remove GO:0006417 from P34707 and to flag UniProtKB keyword KW-0810 for removal from this entry. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine learning annotation for regulation of gene expression. Reason: Accurate but general annotation. SKN-1 regulates expression of Phase II detoxification genes. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:24068940 Integration of the unfolded protein and oxidative stress res... | ACCEPT | Summary: SKN-1 positively regulates transcription of Phase II detoxification genes in response to oxidative and ER stress. Reason: Core molecular function annotation. SKN-1 is a transcriptional activator of stress response genes. Supporting Evidence: PMID:24068940 Sep 12. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. |
| GO:1990748 cellular detoxification | IMP PMID:23721876 The Nrf2/SKN-1-dependent glutathione S-transferase Ο homolog... | ACCEPT | Summary: SKN-1 regulates expression of glutathione S-transferases and other Phase II detoxification enzymes. Reason: Core biological process annotation. SKN-1/Nrf2 is the master regulator of cellular detoxification responses. Supporting Evidence: PMID:23721876 GST-1-mediated neuroprotection is dependent on the PD-associated transcription factor Nrf2/SKN-1, as a reduction in SKN-1 gene expression results in a decrease in GST-1 protein expression |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:28600327 The Oxidative Stress Response in Caenorhabditis elegans Requ... | ACCEPT | Summary: Direct demonstration of SKN-1 DNA binding in the context of oxidative stress response. Reason: IDA evidence confirms SKN-1 binds specifically to cis-regulatory regions of target genes. Supporting Evidence: PMID:28600327 2017 Jun 9. The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. |
| GO:0005515 protein binding | IPI PMID:28600327 The Oxidative Stress Response in Caenorhabditis elegans Requ... | MODIFY | Summary: SKN-1 interacts with ELT-3 (GATA transcription factor) to co-activate target gene transcription. Reason: Protein binding is too general. SKN-1 has specific protein interactions with transcriptional regulators like ELT-3. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:28600327 2017 Jun 9. The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. |
| GO:0005634 nucleus | IDA PMID:28600327 The Oxidative Stress Response in Caenorhabditis elegans Requ... | ACCEPT | Summary: IDA evidence for nuclear localization of SKN-1 isoforms B and C during oxidative stress response. Reason: Consistent with other nuclear localization annotations. Supporting Evidence: PMID:28600327 2017 Jun 9. The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. |
| GO:0008340 determination of adult lifespan | IMP PMID:28600327 The Oxidative Stress Response in Caenorhabditis elegans Requ... | ACCEPT | Summary: SKN-1 activity extends lifespan in C. elegans. Reason: Core biological process annotation. SKN-1's role in longevity is well-established. Supporting Evidence: PMID:28600327 2017 Jun 9. The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:28600327 The Oxidative Stress Response in Caenorhabditis elegans Requ... | ACCEPT | Summary: SKN-1 positively regulates transcription of gst-4 and other Phase II detoxification genes. Reason: Valid experimental evidence for this core function. Supporting Evidence: PMID:28600327 2017 Jun 9. The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. |
| GO:0005634 nucleus | IDA PMID:34407394 Tribbles pseudokinase NIPI-3 regulates intestinal immunity i... | ACCEPT | Summary: Nuclear localization of SKN-1 demonstrated in context of innate immunity responses. Reason: Confirms nuclear localization during pathogen infection. Supporting Evidence: PMID:34407394 Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity. |
| GO:0042742 defense response to bacterium | IMP PMID:34407394 Tribbles pseudokinase NIPI-3 regulates intestinal immunity i... | ACCEPT | Summary: SKN-1 is required for intestinal defense against bacterial pathogens. Reason: Important biological process annotation. SKN-1 integrates oxidative stress and innate immunity responses. Supporting Evidence: PMID:34407394 Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity. |
| GO:0048565 digestive tract development | IMP PMID:1547503 skn-1, a maternally expressed gene required to specify the f... | ACCEPT | Summary: SKN-1 is required for specification of mesendoderm during embryogenesis, which gives rise to pharynx and intestine. Reason: Core developmental function annotation. Supporting Evidence: PMID:1547503 skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. |
| GO:0048566 embryonic digestive tract development | IMP PMID:1547503 skn-1, a maternally expressed gene required to specify the f... | ACCEPT | Summary: More specific annotation for SKN-1's role in embryonic gut development. Reason: Appropriately specific developmental annotation. Supporting Evidence: PMID:1547503 skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. |
| GO:0010468 regulation of gene expression | IMP PMID:26016853 The Developmental Intestinal Regulator ELT-2 Controls p38-De... | ACCEPT | Summary: SKN-1 regulates expression of innate immunity genes in the adult intestine. Reason: General annotation but accurate. Supporting Evidence: PMID:26016853 SKN-1/Nrf, better known for regulating oxidative stress responses, was further found to contribute to resistance against bacterial pathogens |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:26016853 The Developmental Intestinal Regulator ELT-2 Controls p38-De... | ACCEPT | Summary: SKN-1 contributes to defense against Gram-negative bacteria like P. aeruginosa. Reason: Specific innate immunity annotation supported by experimental evidence. Supporting Evidence: PMID:26016853 SKN-1/Nrf, better known for regulating oxidative stress responses, was further found to contribute to resistance against bacterial pathogens |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:24068940 Integration of the unfolded protein and oxidative stress res... | ACCEPT | Summary: Direct demonstration of SKN-1 binding to regulatory regions of target genes. Reason: IDA evidence for specific DNA binding to transcription regulatory regions. Supporting Evidence: PMID:24068940 Sep 12. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: Seminal paper demonstrating SKN-1 activates Phase II detoxification genes in response to oxidative stress. Reason: Key publication establishing SKN-1's role as transcriptional activator. Supporting Evidence: PMID:12869585 SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:25688864 Investigating the role of RIO protein kinases in Caenorhabdi... | ACCEPT | Summary: SKN-1 positively regulates transcription of riok-1 in the intestine. Reason: Additional experimental evidence for SKN-1's transcriptional activator function. Supporting Evidence: PMID:25688864 eCollection 2015. Investigating the role of RIO protein kinases in Caenorhabditis elegans. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: Direct demonstration of SKN-1 binding to gcs-1 regulatory region. Reason: IDA evidence from seminal paper on SKN-1 function. Supporting Evidence: PMID:12869585 SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:24453991 Regulation of synaptic nlg-1/neuroligin abundance by the skn... | ACCEPT | Summary: SKN-1 binds to regulatory regions of nlg-1/neuroligin to regulate its expression. Reason: IDA evidence for SKN-1 DNA binding with a novel target gene. Supporting Evidence: PMID:24453991 2014 Jan 16. Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress. |
| GO:0030544 Hsp70 protein binding | IPI PMID:24068940 Integration of the unfolded protein and oxidative stress res... | ACCEPT | Summary: SKN-1 interacts with Hsp70 family members (hsp-4) during integration of ER stress and oxidative stress responses. Reason: Specific protein interaction annotation. HSP-4 interaction is relevant to SKN-1A's role in ER/proteasome stress responses. Supporting Evidence: PMID:24068940 Sep 12. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. |
| GO:0036498 IRE1-mediated unfolded protein response | IEP PMID:24068940 Integration of the unfolded protein and oxidative stress res... | KEEP AS NON CORE | Summary: SKN-1 expression/activity is modulated by IRE1 branch of UPR. Reason: SKN-1 participates in UPR but this represents an integration point rather than core function. Supporting Evidence: PMID:24068940 Sep 12. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. |
| GO:0036500 ATF6-mediated unfolded protein response | IDA PMID:26232625 SKN-1/Nrf, stress responses, and aging in Caenorhabditis ele... | KEEP AS NON CORE | Summary: SKN-1 integrates with ATF6 branch of UPR based on review of stress response integration. Reason: Represents integration of stress pathways rather than core SKN-1 function. Supporting Evidence: PMID:26232625 SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. |
| GO:0010628 positive regulation of gene expression | IMP PMID:23721876 The Nrf2/SKN-1-dependent glutathione S-transferase Ο homolog... | ACCEPT | Summary: SKN-1 positively regulates expression of GST-1 and other detoxification genes. Reason: Accurate annotation. SKN-1 activates expression of Phase II detoxification genes. Supporting Evidence: PMID:23721876 a reduction in SKN-1 gene expression results in a decrease in GST-1 protein expression |
| GO:1905804 positive regulation of cellular response to manganese ion | IMP PMID:23721876 The Nrf2/SKN-1-dependent glutathione S-transferase Ο homolog... | KEEP AS NON CORE | Summary: SKN-1 protects against manganese toxicity by activating detoxification genes. Reason: This represents a specific application of SKN-1's general detoxification function. Supporting Evidence: PMID:23721876 a Caenorhabditis elegans GSTpi homologue, GST-1, inhibits Mn-induced DA neuron degeneration |
| GO:1905804 positive regulation of cellular response to manganese ion | IGI PMID:23721876 The Nrf2/SKN-1-dependent glutathione S-transferase Ο homolog... | KEEP AS NON CORE | Summary: Genetic interaction evidence for SKN-1's role in manganese response. Reason: Same term with different evidence code. Represents specific stress context. Supporting Evidence: PMID:23721876 2013 May 27. The Nrf2/SKN-1-dependent glutathione S-transferase Ο homologue GST-1 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of manganism. |
| GO:1901562 response to paraquat | IGI PMID:19783783 Life-span extension by dietary restriction is mediated by NL... | KEEP AS NON CORE | Summary: SKN-1 is required for response to paraquat-induced oxidative stress. Reason: Paraquat is a specific oxidative stressor. The core function is response to oxidative stress more generally. Supporting Evidence: PMID:19783783 Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. |
| GO:0008340 determination of adult lifespan | IGI PMID:19783783 Life-span extension by dietary restriction is mediated by NL... | ACCEPT | Summary: Genetic interaction evidence for SKN-1 in lifespan determination, specifically in context of dietary restriction. Reason: Core biological process. SKN-1 promotes longevity through multiple mechanisms. Supporting Evidence: PMID:19783783 Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. |
| GO:0048566 embryonic digestive tract development | IGI PMID:25819561 Centrosome-Associated Degradation Limits Ξ²-Catenin Inheritan... | ACCEPT | Summary: Genetic interaction demonstrating SKN-1's role in embryonic gut specification. Reason: Core developmental function. Maternal SKN-1 specifies mesendoderm fate. Supporting Evidence: PMID:25819561 2015 Mar 26. Centrosome-Associated Degradation Limits Ξ²-Catenin Inheritance by Daughter Cells after Asymmetric Division. |
| GO:0001714 endodermal cell fate specification | IMP PMID:25819561 Centrosome-Associated Degradation Limits Ξ²-Catenin Inheritan... | ACCEPT | Summary: SKN-1 specifies endodermal cell fates through activation of downstream transcription factors. Reason: Core developmental function. SKN-1 activates MED-1/2 which in turn activate END-1/3 for endoderm specification. Supporting Evidence: PMID:25819561 2015 Mar 26. Centrosome-Associated Degradation Limits Ξ²-Catenin Inheritance by Daughter Cells after Asymmetric Division. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:9303538 SKN-1 domain folding and basic region monomer stabilization ... | ACCEPT | Summary: Biochemical demonstration of SKN-1's sequence-specific DNA binding through its unique Skn domain. Reason: Core molecular function. SKN-1 binds DNA as a monomer through a unique mechanism. Supporting Evidence: PMID:9303538 SKN-1 domain folding and basic region monomer stabilization upon DNA binding. |
| GO:0005783 endoplasmic reticulum | IDA PMID:24068940 Integration of the unfolded protein and oxidative stress res... | ACCEPT | Summary: SKN-1A isoform localizes to the ER via N-terminal transmembrane domain. Reason: Accurate isoform-specific localization. SKN-1A is ER-associated. Supporting Evidence: PMID:24068940 Sep 12. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. |
| GO:0000303 response to superoxide | IEP PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: SKN-1 expression/activity is induced by superoxide/oxidative stress. Reason: Core stress response function. SKN-1 is activated by and protects against oxidative stress. Supporting Evidence: PMID:12869585 skn-1 mutants are sensitive to oxidative stress and have shortened lifespans |
| GO:0000303 response to superoxide | IMP PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: SKN-1 is required for proper response to superoxide stress. Reason: IMP evidence for same term. Both evidence codes are appropriate. Supporting Evidence: PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. |
| GO:0005634 nucleus | IDA PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: Nuclear localization of SKN-1 in ASI neurons and intestinal cells during stress response. Reason: Key publication demonstrating stress-induced nuclear translocation. Supporting Evidence: PMID:12869585 SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress |
| GO:0006979 response to oxidative stress | IEP PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: SKN-1 expression/activity is induced by oxidative stress. Reason: Core biological process annotation. SKN-1 is the master regulator of oxidative stress responses in C. elegans. Supporting Evidence: PMID:12869585 SKN-1 functions similarly to resist oxidative stress in C. elegans |
| GO:0008340 determination of adult lifespan | IMP PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | ACCEPT | Summary: SKN-1 mutants have shortened lifespan, demonstrating its role in longevity. Reason: Core phenotype. SKN-1 promotes longevity through stress resistance. Supporting Evidence: PMID:12869585 skn-1 mutants are sensitive to oxidative stress and have shortened lifespans |
| GO:0009408 response to heat | IEP PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a cons... | KEEP AS NON CORE | Summary: SKN-1 activity is induced by heat stress. Reason: Heat stress response is one of many stress contexts where SKN-1 is activated, but oxidative stress response is the core function. Supporting Evidence: PMID:12869585 SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. |
| GO:0005739 mitochondrion | IDA PMID:23040073 Mitochondrial SKN-1/Nrf mediates a conserved starvation resp... | ACCEPT | Summary: SKN-1A isoform localizes to mitochondria where it interacts with PGAM-5. Reason: Isoform-specific localization with functional significance for metabolic stress responses. Supporting Evidence: PMID:23040073 Mitochondrial SKN-1/Nrf mediates a conserved starvation response. |
| GO:0005634 nucleus | IDA PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: Nuclear localization demonstrated in context of p38 MAPK regulation. Reason: Key publication showing PMK-1-dependent nuclear translocation. Supporting Evidence: PMID:16166371 In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei |
| GO:0008340 determination of adult lifespan | IMP PMID:22560223 TOR signaling and rapamycin influence longevity by regulatin... | ACCEPT | Summary: SKN-1 mediates lifespan extension by rapamycin and reduced TOR signaling. Reason: Core longevity function. SKN-1 is required for lifespan extension in multiple genetic and pharmacological contexts. Supporting Evidence: PMID:22560223 TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. |
| GO:1900409 positive regulation of cellular response to oxidative stress | IMP PMID:22560223 TOR signaling and rapamycin influence longevity by regulatin... | ACCEPT | Summary: SKN-1 positively regulates oxidative stress responses downstream of TOR signaling. Reason: Core function. SKN-1 activates protective stress response programs. Supporting Evidence: PMID:22560223 TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. |
| GO:0048382 mesendoderm development | IMP PMID:1547503 skn-1, a maternally expressed gene required to specify the f... | ACCEPT | Summary: SKN-1 is required for mesendoderm specification in early embryogenesis. Reason: Core developmental function. This is the original embryonic function described for SKN-1. Supporting Evidence: PMID:1547503 skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. |
| GO:0001714 endodermal cell fate specification | IGI PMID:15979606 Genetic redundancy in endoderm specification within the genu... | ACCEPT | Summary: Genetic interactions with end-1 and end-3 for endoderm specification. Reason: Core developmental function. SKN-1 acts upstream of END-1/3 GATA factors. Supporting Evidence: PMID:15979606 Genetic redundancy in endoderm specification within the genus Caenorhabditis. |
| GO:0008340 determination of adult lifespan | IGI PMID:20523893 Manipulation of behavioral decline in Caenorhabditis elegans... | ACCEPT | Summary: Genetic interaction evidence for SKN-1 in lifespan regulation. Reason: Additional genetic evidence for core longevity function. Supporting Evidence: PMID:20523893 Manipulation of behavioral decline in Caenorhabditis elegans with the Rag GTPase raga-1. |
| GO:0005515 protein binding | IPI PMID:19273594 The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ... | MODIFY | Summary: SKN-1 interacts with WDR-23, the adaptor for CUL4/DDB1 ubiquitin ligase that targets SKN-1 for degradation. Reason: Protein binding is too general. WDR-23 is a specific regulatory interaction. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19273594 Mar 9. The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. |
| GO:0008340 determination of adult lifespan | IMP PMID:18358814 Direct inhibition of the longevity-promoting factor SKN-1 by... | ACCEPT | Summary: SKN-1 promotes longevity when insulin-like signaling is reduced or when SKN-1 is constitutively active. Reason: Seminal paper demonstrating SKN-1's role in longevity downstream of insulin/IGF-1 signaling. Supporting Evidence: PMID:18358814 Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:9628487 A new DNA-binding motif in the Skn-1 binding domain-DNA comp... | ACCEPT | Summary: Crystal structure demonstrates SKN-1's unique DNA-binding mechanism. Reason: Structural evidence for DNA binding mechanism. Supporting Evidence: PMID:9628487 A new DNA-binding motif in the Skn-1 binding domain-DNA complex. |
| GO:0005634 nucleus | IDA PMID:8348611 The maternal gene skn-1 encodes a protein that is distribute... | ACCEPT | Summary: Early demonstration of SKN-1 nuclear localization in embryos. Reason: Original publication on SKN-1 protein localization. Supporting Evidence: PMID:8348611 The maternal gene skn-1 encodes a protein that is distributed unequally in early C. |
| GO:0001708 cell fate specification | IMP PMID:8861906 Spatial and temporal controls target pal-1 blastomere-specif... | ACCEPT | Summary: SKN-1 specifies cell fates during early embryonic patterning. Reason: Core developmental function. Supporting Evidence: PMID:8861906 Spatial and temporal controls target pal-1 blastomere-specification activity to a single blastomere lineage in C. |
| GO:0009880 embryonic pattern specification | IMP PMID:8861906 Spatial and temporal controls target pal-1 blastomere-specif... | ACCEPT | Summary: SKN-1 contributes to embryonic pattern specification along with PAL-1. Reason: Core developmental function. SKN-1 is part of the maternal gene network that patterns the early embryo. Supporting Evidence: PMID:8861906 Spatial and temporal controls target pal-1 blastomere-specification activity to a single blastomere lineage in C. |
| GO:0003700 DNA-binding transcription factor activity | NAS PMID:1547503 skn-1, a maternally expressed gene required to specify the f... | ACCEPT | Summary: Original publication identifying SKN-1 as transcription factor. Reason: NAS from original discovery paper. Later confirmed by extensive experimental evidence. Supporting Evidence: PMID:1547503 skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. |
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Download this section (compressed HTML)Q: What are the specific DNA binding sites and target gene repertoires for each SKN-1 isoform?
Q: How does SKN-1 coordinate with other stress-responsive transcription factors like DAF-16 and HSF-1?
Q: What determines whether SKN-1 activates oxidative stress genes versus innate immunity genes?
Experiment: ChIP-seq analysis comparing SKN-1 binding sites under different stress conditions
Experiment: Isoform-specific RNA-seq to distinguish SKN-1A, B, and C target genes
Experiment: Genetic screens for additional SKN-1 regulators in the WDR-23-independent pathway
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