Fbxo31-flox Mouse

Fbxo31, a member of the F-box family that comprises the SCF complex, is involved in regulating protein ubiquitination and degradation, which is crucial for various biological processes such as cell growth, migration, and invasion [1-7]. It participates in multiple pathways, like the METTL3-FBXO31-SIRT2 axis in pancreatic cancer, the FBXO31-GPX4 interaction in cholangiocarcinoma, and the c-Myc-FBXO31 feedback regulation in ovarian cancer [1,2,4]. Genetic models are valuable for studying its functions.

In pancreatic cancer, FBXO31 is overexpressed, promoting tumor growth, migration, and invasion by regulating SIRT2 ubiquitination and degradation. METTL3 up-regulates FBXO31 expression through m6A modification [1].

In cholangiocarcinoma, FBXO31 is downregulated, and its deficiency is associated with the TNM stage. Overexpression of FBXO31 inhibits cell growth, migration, and cancer stem cell properties, and sensitizes cancer stem-like cells to cisplatin by promoting ferroptosis and GPX4 degradation [2].

In glioma, low FBXO31 expression indicates poor prognosis, and its overexpression suppresses lipogenesis and tumor progression by promoting CD147 ubiquitination and degradation [3].

In ovarian cancer, c-Myc suppresses FBXO31 mRNA levels, while FBXO31 facilitates c-Myc polyubiquitination and degradation, inhibiting ovarian cancer growth [4].

In prostate cancer, low FBXO31 mRNA levels are associated with high pre-operative prostate-specific antigen levels and Gleason grade. FBXO31 promotes DUSP6 degradation, and its depletion dysregulates ERK and PI3K-AKT signaling, promoting tumor development [5].

In esophageal squamous cell carcinoma, high FBXO31 expression is associated with poor prognosis and Taxol chemoresistance. Silencing FBXO31 sensitizes cells to Taxol, and this effect is associated with cofilin-1 [6].

In liver fibrosis, FBXO31 is upregulated, and it modulates hepatic stellate cell activation and liver fibrogenesis by promoting Smad7 ubiquitination [7].

In conclusion, FBXO31 plays diverse roles in regulating biological processes and is involved in multiple disease conditions such as various cancers, premature ovarian insufficiency, and liver fibrosis. Functional studies, especially those using knockout or conditional knockout mouse models (implied by in vivo experiments in references), have revealed its significance in tumorigenesis, cell-specific functions, and disease-associated pathways, providing potential therapeutic targets for these diseases.