| Category | Finding | System/cancer type | Evidence type | Citation IDs | URL and year |
|---|---|---|---|---|---|
| Identity / complex | Human FBXL7 (UniProt Q9UJT9) is a 491-aa FBXL-family F-box protein that serves as the substrate-recognition subunit of SCF (SKP1–CUL1–RBX1–F-box) E3 ubiquitin ligases | Human | Review synthesizing primary studies | (pqac-00000003, pqac-00000006) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Domains | FBXL7 contains an N-terminal F-box motif for SKP1 binding and ~11 C-terminal leucine-rich repeats (LRRs); review also notes an N-terminal serine-rich region | Human | Review / structural-functional annotation | (pqac-00000003, pqac-00000006) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Validated substrate | AURKA/Aurora A is a canonical FBXL7 substrate; FBXL7 promotes AURKA polyubiquitylation and turnover, causing centrosomal degradation during mitosis | Cell cycle / mitotic models; cancer context | Primary biochemical/cell biology summarized in review | (pqac-00000003, pqac-00000006) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Phenotypic output | AURKA degradation by FBXL7 is linked to spindle defects, polyploidy, G2/M arrest, and mitotic arrest | Mitotic models | Primary functional studies summarized in review | (pqac-00000003, pqac-00000006) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Localization / pathway note | FBXL7 colocalizes with Aurora A and targets it for centrosomal degradation during mitosis | Mitotic models | Primary cell biology summarized in review | (pqac-00000003) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Validated substrate | BIRC5/survivin is directly recognized by SCF-FBXL7 and degraded by the proteasome | Lung epithelial cells / broad cell biology | Primary biochemical study | (pqac-00000004, pqac-00000005, pqac-00000007) | https://doi.org/10.1074/jbc.m114.629931 (2015) |
| Quantitative finding | Endogenous survivin half-life is ~2 h; MG132 stabilizes survivin decay whereas leupeptin does not | Cell culture | Primary kinetics / inhibitor evidence | (pqac-00000005) | https://doi.org/10.1074/jbc.m114.629931 (2015) |
| Mechanistic detail | Survivin recognition involves residue E126, and Lys90/Lys91 serve as ubiquitin acceptor sites; E126A and K90R/K91R mutants resist FBXL7 effects | Cell culture / biochemical assays | Primary mutational analysis | (pqac-00000004, pqac-00000007) | https://doi.org/10.1074/jbc.m114.629931 (2015) |
| Phenotypic output | FBXL7 overexpression impairs mitochondrial function and promotes apoptosis; survivin counters FBXL7-induced mitochondrial defects | Lung epithelial cells | Primary functional study | (pqac-00000004, pqac-00000007) | https://doi.org/10.1074/jbc.m114.629931 (2015) |
| Quantitative finding | Overexpression of wild-type FBXL7 reduced Mfn1 protein by 36% and lowered ATP in a dose-dependent manner | MLE cells | Primary quantitative cell biology | (pqac-00000005) | https://doi.org/10.1074/jbc.m114.629931 (2015) |
| Validated substrate | Active c-SRC is targeted by FBXL7 after phosphorylation at Ser104, leading to ubiquitylation and proteasomal degradation | Prostate and pancreatic cancer | Primary mechanistic cancer study | (pqac-00000002, pqac-00000003) | https://doi.org/10.1038/s41556-020-0560-6 (2020) |
| Upstream regulation | FBXL7 promoter hypermethylation lowers FBXL7 mRNA/protein in advanced prostate and pancreatic cancers | Prostate and pancreatic cancer | Primary epigenetic/clinical association | (pqac-00000002, pqac-00000013) | https://doi.org/10.1038/s41556-020-0560-6 (2020) |
| Therapeutic modulation | Decitabine restores FBXL7 expression and limits EMT/invasion in a c-SRC-dependent manner; dasatinib suppresses metastasis when FBXL7 is depleted | Prostate and pancreatic cancer | Primary intervention study | (pqac-00000002) | https://doi.org/10.1038/s41556-020-0560-6 (2020) |
| Phenotypic output | FBXL7 acts as a metastasis suppressor by restraining c-SRC-driven EMT and invasion; depletion increases metastatic burden in vivo | Prostate and pancreatic cancer | Primary in vivo functional study | (pqac-00000002) | https://doi.org/10.1038/s41556-020-0560-6 (2020) |
| Validated substrate | SNAI1/Snail1 binds FBXL7 and undergoes ubiquitination/proteasomal degradation | Pancreatic cancer | Primary cancer study | (pqac-00000003) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Phenotypic output | Through Snail1 degradation, FBXL7 suppresses EMT, invasion, and metastasis | Pancreatic cancer | Primary cancer study summarized in review | (pqac-00000003) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Validated substrate | PFKFB4 was identified as an FBXL7 substrate; FBXL7 ubiquitinates and degrades PFKFB4 | NSCLC | Primary 2023 study | (pqac-00000010, pqac-00000011) | https://doi.org/10.1038/s41419-023-05795-z (2023) |
| Upstream regulation | Hypoxia increases HIF-1α, which elevates EZH2; EZH2 represses FBXL7 transcription, stabilizing PFKFB4 and enhancing glycolysis | NSCLC under hypoxia | Primary mechanistic study | (pqac-00000010, pqac-00000011) | https://doi.org/10.1038/s41419-023-05795-z (2023) |
| Phenotypic output | FBXL7 re-expression suppresses viability, migration, invasion, glucose metabolism, and promotes apoptosis; effects are significant across repeated experiments | NSCLC (A549, H1650) | Primary functional study | (pqac-00000008, pqac-00000010) | https://doi.org/10.1038/s41419-023-05795-z (2023) |
| Quantitative finding | Higher PFKFB4 expression is associated with worse survival in lung cancer: HR 1.38, 95% CI 1.17–1.63, log-rank P=0.00012 | LUAD/LUSC datasets | Clinical association within mechanistic paper | (pqac-00000008) | https://doi.org/10.1038/s41419-023-05795-z (2023) |
| Upstream regulation | AURKA negatively regulates FBXL7 at transcriptional and translational levels through a FOXP1–FBXL7 axis, thereby limiting survivin degradation | Gastric cancer | Primary mechanistic cancer study | (pqac-00000001) | https://doi.org/10.7150/thno.42735 (2020) |
| Network effect | AURKA restricts FBXL7-mediated survivin ubiquitylation, contributing to drug resistance | Gastric cancer | Review summarizing primary study | (pqac-00000001) | https://doi.org/10.7150/thno.42735 (2020) |
| Drug-response application | In ovarian cancer, high FBXL7 transcript is associated with poor prognosis and unfavorable paclitaxel response; FBXL7 expression correlates with paclitaxel IC50 across cell lines | Ovarian cancer | Primary translational study summarized in search results | (pqac-00000001) | https://doi.org/10.3390/jcm7100330 (2018) |
| Drug-response mechanism | Dioscin promotes proteasome-dependent survivin degradation by strengthening FBXL7–survivin interaction; FBXL7 knockdown blunts dioscin cytotoxicity | NSCLC | Primary 2024 pharmacology study | (pqac-00000009) | https://doi.org/10.7150/jca.89831 (2024) |
| Quantitative finding | In NSCLC cells, 5 μM dioscin for 72 h reduced viability by >90%; xenograft dosing was 10 mg/kg i.p. every 2 days (n=6/cohort) | NSCLC xenograft and cell lines | Primary 2024 preclinical study | (pqac-00000009) | https://doi.org/10.7150/jca.89831 (2024) |
| Biomarker / epigenetics | FBXL7 gene body hypomethylation is frequent in upper aerodigestive tract tumors, correlates with gene expression, and has high discriminatory potential between tumor and non-tumor tissue | ESCC, OCSCC, LSCC, OPSCC | Primary biomarker study | (pqac-00000012) | https://doi.org/10.3390/ijms23147801 (2022) |
| Figure-based clinicopathology | FBXL7 promoter methylation positively correlates with Gleason grade, pathological stage, and overall disease stage in prostate cancer | Prostate cancer | Figure-derived clinical association | (pqac-00000013) | https://doi.org/10.1038/s41556-020-0560-6 (2020) |
| Expert synthesis | Reviews place FBXL7 at the intersection of apoptosis, mitosis/cell-cycle control, mitochondrial homeostasis, EMT/metastasis, glucose metabolism, and drug response | Human cancers | Expert review | (pqac-00000003, pqac-00000006) | https://doi.org/10.1038/s41420-022-01143-w (2022) |
| Evidence gap / implementation | No FBXL7-targeted clinical trials were retrieved; current real-world implementation is mainly as a candidate biomarker/therapeutic axis rather than a validated drug target | Clinical translation | Negative search finding / evidence synthesis | (pqac-00000000) | Open Targets search context (accessed via tool; latest indexed evidence includes 2023–2024 literature) |


*Table: This table summarizes the core functional annotation of human FBXL7 (UniProt Q9UJT9), including its SCF-complex role, validated substrates, upstream regulators, phenotypic consequences, and key quantitative findings from primary and review literature. It is useful as a compact evidence map for molecular function, pathway context, and translational relevance.*