Fbxo11, also known as VIT1 and PRMT9, is a member of the F-box protein family and serves as the substrate-recognition component of the Skp1-Cullin-1-F-box E3 ubiquitin-ligase complex. It is involved in multiple biological processes, including ubiquitin-dependent proteasomal degradation, which plays a key role in regulating protein levels in various pathways. It is associated with pathways like MHC class II regulation, bone development, lipid metabolism, and immune responses, highlighting its overall biological importance. Genetic models, such as KO/CKO mouse models, have been valuable in studying its functions [1,2].

In osteoblast-specific conditional knockout (CKO) mouse models (Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO), FBXO11 deficiency inhibits normal bone growth. FBXO11 knockdown in mouse pre-osteoblast MC3T3-E1 cells reduces osteogenic differentiation, while overexpression accelerates it. Mechanistically, FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, suppressing osteogenic activity and bone matrix mineralization [2]. In human and mouse FBXO11-deficient cells, increased levels of MHC-II and related genes are observed, and in normal and cancer tissues, FBXO11 expression is negatively correlated with MHC-II. FBXO11 also regulates CIITA protein levels through ubiquitination-mediated degradation, and its expression may serve as a biomarker for cancer [1].

In conclusion, Fbxo11 is crucial in multiple biological processes. The study of Fbxo11 using KO/CKO mouse models has provided insights into its role in bone development and MHC-II regulation, which are relevant to understanding skeletal diseases and cancer immunology. These findings contribute to a better understanding of the underlying mechanisms of related diseases and may offer potential therapeutic targets [1,2].