| Biological context/model (cell type/organism) | Molecular role | Direct substrates/interactors | Downstream pathway effects | Key readouts/quantitative outcomes | Evidence type | Publication (authors, journal) | Year | DOI/URL | Notes/limitations |
|---|---|---|---|---|---|---|---|---|---|
| Lung epithelium; MLE-12 cells / mouse, with human FBXO17 constructs | SCF substrate receptor | GSK3β; Skp1 | Promotes K48-linked proteasomal turnover of GSK3β; dampens pro-inflammatory signaling | FBXO17 overexpression lowers GSK3β protein; FBXO17 silencing increases GSK3β half-life; reduced TNFα/LPS-induced IL-6 and KC/CXCL1; KC suppression partially rescued by GSK3β re-expression (pqac-00000002, pqac-00000007, pqac-00000009, pqac-00000011, pqac-00000013) | Co-IP, IF colocalization, CHX chase, MG132 rescue, ubiquitination assay, siRNA knockdown, cytokine assays (pqac-00000007, pqac-00000008, pqac-00000013) | Suber et al., *J. Biol. Chem.* (pqac-00000002, pqac-00000007) | 2017 | https://doi.org/10.1074/jbc.m116.771667 | Strongest direct mechanistic evidence for FBXO17 as SCF adaptor; primary functional work is in murine lung epithelial cells rather than human tissues (pqac-00000002, pqac-00000007) |
| Antiviral innate immune signaling; mammalian cells / human-focused signaling study | Non-canonical scaffold (SCF-independent for this function) | IRF3; PP2A | Negative regulation of type I IFN signaling via IRF3 dephosphorylation/inactivation | FBXO17 specifically interacts with IRF3 and recruits PP2A; this recruitment uses the F-box-associated region and is reported as independent of canonical SCF E3 ligase function, enhancing IRF3 dephosphorylation and suppressing IFN-I signaling (pqac-00000005) | Interaction assays and signaling/functional immune assays summarized in text evidence (pqac-00000005) | Peng et al., *J. Immunol.* (pqac-00000005) | 2017 | https://doi.org/10.4049/jimmunol.1601009 | Evidence supports a signaling-scaffold role rather than a demonstrated ubiquitin substrate in this context; quantitative effect sizes not available in provided context (pqac-00000005) |
| Lung adenocarcinoma; A549 and other lung cancer cell lines / human | Likely SCF-linked regulator; mechanistically tied to GSK3β turnover | GSK3β; Akt-pathway mediators (PDK1, ERK1/2, RPS6, CREB as downstream readouts) | Activates Akt/ERK/mTOR-related signaling and promotes proliferation/survival | FBXO17 overexpression increases cell number, metabolic activity, and S-phase fraction; increases p-Akt (Thr308, modestly Ser473), PDK1, p-ERK1/2, p-CREB, and p-RPS6; knockdown reduces growth and p-ERK1/2, with trend toward reduced p-Akt Ser473; 212 genes altered after knockdown (pqac-00000004, pqac-00000012) | Overexpression/knockdown, immunoblotting, BrdU/MTS/cell-cycle assays, transcriptomics (pqac-00000012) | Suber et al., *Respir. Res.* (pqac-00000004, pqac-00000012) | 2018 | https://doi.org/10.1186/s12931-018-0910-0 | Direct SCF assembly was not biochemically shown in the provided excerpt; pathway links are strong but substrate causality beyond prior GSK3β work is indirect here (pqac-00000012) |
| Endometrial carcinoma; Ishikawa cells / human | Putative SCF-linked tumor suppressive regulator | Wnt/β-catenin pathway components; β-catenin, GSK3β, pGSK3β measured as affected proteins | Inhibits Wnt/β-catenin signaling; suppresses proliferation and EMT-like changes | FBXO17 overexpression reduces proliferation (CCK-8, RTCA, colony formation, EdU), increases apoptosis and G1 arrest; decreases β-catenin, GSK3β, pGSK3β, cyclin D1, c-Myc, and Axin2 mRNA; increases E-cadherin and decreases N-cadherin (pqac-00000010) | Lentiviral overexpression, proliferation/apoptosis/cell-cycle assays, western blotting, qPCR, bioinformatics pathway analysis (pqac-00000010) | Zheng et al., *Int. J. Med. Sci.* (pqac-00000010) | 2022 | https://doi.org/10.7150/ijms.60335 | Functional evidence is strong for pathway/cell phenotype, but no direct ubiquitination substrate or Co-IP evidence for FBXO17 targets was provided in the excerpt; reported decrease in total GSK3β differs from expectation based on lung studies and may be context-dependent (pqac-00000010) |


*Table: This table summarizes the main experimentally supported functions of human FBXO17 across the four key studies available in context. It separates canonical SCF-associated substrate-receptor activity from non-canonical signaling-scaffold behavior and highlights the strongest evidence, readouts, and study limitations.*