Fbxo22, an F-box protein, is a key component in multiple biological processes. It functions as a substrate receptor of the SCF E3 ligase, participating in ubiquitin-dependent protein degradation, which is crucial for controlling various cellular processes such as cell cycle, transcriptional regulation, and apoptosis [3,4]. It is involved in pathways related to amino acid sensing, carcinogenesis, and more [1,3]. Genetic models like knockout (KO) and conditional knockout (CKO) mouse models are valuable for studying its functions.

In a hematopoietic cell-specific Fbxo22 knockout mouse model, conditional deletion of Fbxo22 did not significantly affect normal hematopoietic stem cell function, but it dramatically abrogated MLL-AF9-induced leukemogenesis and reduced leukemia stem cells after serial transplantations. This shows that Fbxo22 promotes MLL-rearranged acute myeloid leukemia (AML) progression by targeting BACH1 for degradation [2].

In conclusion, Fbxo22 plays essential roles in amino acid sensing via the tRNA-GCN2-Fbxo22-mTOR pathway and in carcinogenesis, especially in promoting the development of certain cancers like AML. The use of KO/CKO mouse models has revealed its specific contributions to leukemogenesis, highlighting its potential as a therapeutic target in this disease area [1,2].