| Substrate/Process | Evidence type (binding/ubiquitination/degradation/phenotype) | Cell/tissue context | Subcellular localization of FBXO10 action | Key mechanistic notes (e.g., SCF complex, PTM required) | Primary citation (author-year, DOI URL, pub date) |
|---|---|---|---|---|---|
| BCL2 | Binding to BCL2; promotion of BCL2 ubiquitination; accelerated degradation/shortened half-life; apoptosis induction in lymphoma cells; hypomorphic cancer mutations reduce activity | Human DLBCL and mantle cell lymphoma cell lines; lymphoma tumor context | Predominantly cytoplasmic, acting on mitochondrial outer membrane-associated/anti-apoptotic BCL2 pool | FBXO10 is the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ligase; intact F-box needed for SKP1 binding/SCF assembly; tumor mutations include R44H (F-box), V762L and R825W (CASH/PbH1 region), impairing BCL2 destabilization; reduced FBXO10 expression/mutation linked to elevated BCL2 and survival signaling (pqac-00000001, pqac-00000003, pqac-00000004, pqac-00000005, pqac-00000010, pqac-00000011, pqac-00000014) | Chiorazzi et al. 2013, https://doi.org/10.1073/pnas.1217271110, Feb 2013; Li et al. 2016, https://doi.org/10.1038/onc.2016.155, Dec 2016 |
| RAGE | FBXO10 identified in F-box screen; binding/association with RAGE; increased ubiquitination; enhanced degradation rate in cycloheximide chase; stabilization after FBXO10 knockdown | Human cell culture models studying inflammatory receptor turnover | Endomembrane/lysosomal pathway after receptor internalization | FBXO10 associates with SKP1/CUL1 consistent with SCF complex; RAGE recognition depends on cytoplasmic K374 and phosphorylation-sensitive S391; ODN2006 and PKCζ signaling promote degradation; reported endpoint is lysosomal degradation rather than classic solely proteasomal turnover (pqac-00000002, pqac-00000006) | Evankovich et al. 2017, https://doi.org/10.1096/fj.201700031r, Sep 2017 |
| PGAM5 | OMM-dependent binding; polyubiquitylation detected by TUBE pulldown; timed degradation during differentiation; loss of FBXO10 impairs mitochondrial ATP production, membrane potential, morphology, mitophagy resolution, and myotube formation | Human iPSC-derived myogenic cells, HeLa localization systems, murine C2C12 myoblast differentiation models | Outer mitochondrial membrane (OMM) | Major 2024 advance: FBXO10 is geranylgeranylated at C953 in a C-terminal CaaX motif; this PTM is required for OMM targeting via PDE6δ/HSP90/TOM70-linked delivery; WT but not C953S mutant localizes to mitochondria and assembles mitochondrial SCF(FBXO10); cullin neddylation/proteasome activity required for PGAM5 turnover (pqac-00000025, pqac-00000026, pqac-00000027, pqac-00000028, pqac-00000029, pqac-00000030, pqac-00000031, pqac-00000040) | Bhat et al. 2024, https://doi.org/10.1016/j.celrep.2024.114783, Oct 2024 |
| ACSL4 | Increased FBXO10 expression downstream of CYP1B1/20-HETE/PKC; ACSL4 polyubiquitination and reduced half-life/protein abundance; ferroptosis suppression; reduced anti-PD-1 response in vivo when pathway is active | Colorectal cancer cell lines and mouse tumor models | Not definitively localized in the cited study; function inferred in cytoplasmic/endomembrane protein quality-control context affecting lipid metabolism | Study places FBXO10 in a CYP1B1 → 20-HETE → PKC → FBXO10 axis; elevated FBXO10 promotes ACSL4 degradation, lowering ferroptosis sensitivity and contributing to immunotherapy resistance; evidence for FBXO10 as ACSL4 E3 is strong but upstream signaling focus is on CYP1B1 (pqac-00000033, pqac-00000034, pqac-00000035, pqac-00000036) | Chen et al. 2023, https://doi.org/10.1038/s41419-023-05803-2, Apr 2023 |
| HGAL | Review-based summary of prior experimental work: BCR-triggered FBXO10 relocalization enables HGAL binding, ubiquitination, and proteasomal degradation | Germinal-center B cells / DLBCL and Burkitt lymphoma signaling context after BCR engagement | Plasma membrane/cell membrane-associated compartment after BCR stimulation, followed by cytoplasmic proteasomal turnover | FBXO10 undergoes rapid, reversible palmitoylation after BCR engagement; palmitoylation drives relocation to the plasma membrane where FBXO10 binds HGAL; interaction reported as phosphorylation-independent and dependent on HGAL H91; included here as review-supported rather than directly re-read primary data in current context (pqac-00000038, pqac-00000039) | Jiang & Lossos 2023, https://doi.org/10.37349/ei.2023.00097, Jun 2023 |
| Mitochondrial proteostasis / myogenic differentiation (process-level) | Comparative mitochondrial proteomics; localization assays; respiration, membrane potential, mitophagy, morphology, and differentiation phenotypes | Human and murine myogenic models | Outer mitochondrial membrane | FBXO10 acts as a prenylated mitochondrial SCF E3 controlling selective OMM proteostasis; ~18 candidate OMM/OMM-associated proteins changed reciprocally with WT versus C953S FBXO10, indicating broader substrate scope beyond PGAM5; WT promotes hyperfused/perinuclear mitochondrial networks, whereas prenylation-deficient or ΔF-box forms act dominantly negative (pqac-00000025, pqac-00000026, pqac-00000028, pqac-00000029, pqac-00000032) | Bhat et al. 2024, https://doi.org/10.1016/j.celrep.2024.114783, Oct 2024 |


*Table: This table summarizes experimentally supported or review-supported FBXO10 substrates/processes, the kinds of evidence behind each assignment, and the cellular compartment where FBXO10 acts. It is useful for distinguishing well-established lymphoma-related roles from newer 2023-2024 findings in mitochondrial proteostasis and ferroptosis-related pathways.*