Fbxo31-KO Mouse

Fbxo31, a member of the F-box family that constitutes the SCF complex, plays a crucial role in various biological processes. It is involved in ubiquitination-mediated protein degradation, which is essential for regulating multiple cellular pathways such as cell growth, migration, invasion, and redox biology [1,2,3,4,6,7,8,9]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying Fbxo31's functions.

In cancer research, FBXO31 shows diverse roles. In pancreatic cancer, it is upregulated by METTL3, promoting cancer progression via regulating SIRT2 ubiquitination and degradation [1]. In contrast, in cholangiocarcinoma, glioma, ovarian cancer, and prostate cancer, its deficiency or down-regulation is associated with tumor initiation, progression, and poor prognosis. For example, in cholangiocarcinoma, FBXO31 functions as a tumor suppressor, sensitizing cancer stem-like cells to cisplatin by promoting ferroptosis and facilitating the proteasomal degradation of GPX4 [2]. In glioma, it suppresses lipogenesis and tumor progression by promoting ubiquitination and degradation of CD147 [3]. In ovarian cancer, c-Myc represses FBXO31 transcription, while FBXO31 facilitates c-Myc polyubiquitination to inhibit cancer growth [6]. In prostate cancer, loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling, promoting tumorigenesis [9]. In esophageal squamous cell carcinoma, high expression of FBXO31 is related to Taxol chemoresistance [7]. Additionally, in premature ovarian insufficiency, aberrantly high FBXO31 in granulosa cells impairs oocyte quality [5]. In liver fibrosis, FBXO31 upregulation promotes hepatic stellate cell activation and fibrogenesis by enhancing Smad7 ubiquitination [8].

In conclusion, Fbxo31 is a key regulator in multiple biological processes, especially in tumorigenesis and cancer progression. Studies using KO/CKO mouse models have revealed its significance in various disease areas, including different types of cancers, premature ovarian insufficiency, and liver fibrosis. Understanding Fbxo31's functions provides potential therapeutic targets for these diseases.