| Substrate/Interactor | Evidence type (co-IP, ubiquitination, degradation, functional assay) | Ubiquitin linkage / degradation mechanism | Required FBXO16 domain(s) | Cellular compartment | Biological context (cell type/cancer) | Key quantitative data (n, fold-changes, p-values) | Publication (authors, journal, year, date) | URL | Citation context ID |
|---|---|---|---|---|---|---|---|---|---|
| β-catenin (CTNNB1) | IP/co-IP interaction in RANG-2 and LN229; nuclear-fraction ubiquitination assays; MG132 rescue; TOPFlash Wnt reporter; migration/proliferation/xenograft assays | K48-linked polyubiquitination of nuclear β-catenin followed by proteasome-dependent degradation; reported GSK3β-independent | C-terminal region required for β-catenin interaction; ΔC loses binding, while ΔF and N-terminal deletion retain interaction | Predominantly nuclear β-catenin pool | Human glioblastoma models (RANG-2, LN229; xenografts) | ~4-fold reduction in nuclear RFP-β-catenin speckles with FBXO16 overexpression; ~30% reduced migration (P≤0.008); decreased TOPFlash, c-Myc, Cyclin D1; qRT-PCR cohort glioma n=11 vs normal brain n=4; xenograft tumor volume ~800 mm^3 ±71.6 in model context; n=3 for some assays, P≤0.001 | Khan, Muzumdar, Shiras; *Neoplasia*; 2019; Jan | https://doi.org/10.1016/j.neo.2018.11.005 | (pqac-00000011, pqac-00000012, pqac-00000015, pqac-00000016) |
| hnRNPL | BioGRID-guided candidate identification; co-IP and GST pull-down; TUBE2 ubiquitination enrichment; CHX half-life; MG132 rescue; in vitro ubiquitination with Cul1-Skp1-Rbx1 + FBXO16; rescue/phenocopy functional assays | SCF/CUL1-SKP1-RBX1-dependent ubiquitination and proteasomal degradation of hnRNPL | F-box required for ubiquitination activity; C-terminal region required for substrate recognition; binds hnRNPL RRM3 domain | FBXO16 reported mainly nuclear; hnRNPL mainly nuclear | Human ovarian cancer cells; SKOV3 xenograft | Negative FBXO16-hnRNPL correlation in 68 ovarian cancer specimens (χ²=14.81, P<0.001); hnRNPL ΔRRM3 xenograft using 1×10^7 cells, n=5 mice, significantly increased tumor growth (P<0.001); FBXO16 loss increased proliferation, clonogenicity, invasion | Ji et al.; *Cell Death & Disease*; 2021; Jul | https://doi.org/10.1038/s41419-021-04040-9 | (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000009) |
| ULK1 | Co-IP/in vitro interaction; ubiquitination assays; FBXO16 knockdown/overexpression; autophagy and proliferation assays; truncation-mutant testing | K48-linked polyubiquitination of ULK1 with proteasomal targeting; FBXO16 suppresses ULK1-dependent autophagy | C-terminal region implicated based on ΔCTD testing in binding and functional assays | Not explicitly localized in excerpt; mechanism studied in cellular protein turnover/autophagy context | Human high-grade serous ovarian cancer models | FBXO16 knockdown increased ULK1 protein while not affecting ATG7/ATG13/Beclin-1; FBXO16 overexpression decreased ULK1, lowered LC3II/I ratio, increased p62; no cohort HR/effect size reported in excerpt | Zhang et al.; *Cell Death & Disease*; 2024; Oct | https://doi.org/10.1038/s41419-024-07120-8 | (pqac-00000010) |
| NF-κB p65 (RELA) | siRNA screen of 39 Fbxo genes; co-IP with PDLIM2/CUL1/SKP1; polyubiquitination assays; nuclear fractionation; ELAM-1 luciferase; knockdown/deficiency functional assays | Polyubiquitination and proteasomal degradation of p65 within a PDLIM2-containing CRL1/SCF-like complex; loss of Fbxo16 increases nuclear p65 and inflammatory cytokines | F-box domain required for CUL1/PDLIM2 complex formation and p65 polyubiquitination; ΔF mutant impaired | Nuclear/intranuclear, including insoluble nuclear fraction | Dendritic cells; HEK293T, BMDCs, MEFs; inflammatory signaling rather than cancer | Screened 39 Fbxo genes; Fbxo16 deficiency caused striking augmentation of LPS-induced IL-6 and enhanced nuclear p65; WT but not ΔF suppressed NF-κB luciferase activity; no hazard ratios reported | Sugimoto-Ishige, Jodo, Tanaka; *Frontiers in Immunology*; 2025; Jun | https://doi.org/10.3389/fimmu.2025.1524110 | (pqac-00000004, pqac-00000005, pqac-00000007, pqac-00000008, pqac-00000013) |
| SKP1 / CUL1 / RBX1 (SCF components) | Interaction/co-complex evidence; in vitro ubiquitination with Cul1-Skp1-Rbx1 plus FBXO16; co-IP with CUL1/SKP1; dominant-negative CUL1 effects | Supports FBXO16 as the substrate-recognition module of canonical SCF/CRL1 E3 ligase rather than a substrate itself | F-box domain mediates SCF assembly/function | Nuclear context emphasized in ovarian cancer and p65 studies; broader cytoplasmic+nuclear localization also reported | Human ovarian cancer cells; HEK293T; dendritic cell signaling | Dominant-negative CUL1 caused hnRNPL accumulation; Fbxo16 binds CUL1/SKP1 but not CUL2/CUL3 in immune study; quantitative interaction values not provided | Ji et al.; *Cell Death & Disease*; 2021; Jul; Sugimoto-Ishige et al.; *Frontiers in Immunology*; 2025; Jun | https://doi.org/10.1038/s41419-021-04040-9 ; https://doi.org/10.3389/fimmu.2025.1524110 | (pqac-00000002, pqac-00000003, pqac-00000005) |
| PDLIM2 | Co-IP/complex assembly evidence in p65-targeting study | Partner in a PDLIM2-containing CRL1 complex that enables p65 recruitment, polyubiquitination, and degradation | F-box domain needed for proper complex formation with CUL1/PDLIM2 | Nuclear/intranuclear | Dendritic cells; HEK293T reconstitution system | Fbxo16 knockdown was the key hit reverting PDLIM2-dependent p65 decrease in screen-derived follow-up; no explicit effect size in excerpt | Sugimoto-Ishige, Jodo, Tanaka; *Frontiers in Immunology*; 2025; Jun | https://doi.org/10.3389/fimmu.2025.1524110 | (pqac-00000004, pqac-00000005, pqac-00000006) |


*Table: This table compiles experimentally supported evidence for human FBXO16 (UniProt Q8IX29), emphasizing validated substrates, SCF/CRL1 complex partners, domain requirements, compartment, biological context, and quantitative findings. It is useful as a compact functional-annotation map grounded in primary literature and citeable context IDs.*