F-box and leucine-rich repeat protein 6 (FBXL6)

F-box and leucine-rich repeat protein 6 (FBXL6) is a member of the F-box protein family, defined by its F-box motif and leucine-rich repeats, that functions as a substrate-recognition subunit in the SKP1-cullin-F-box (SCF) E3 ubiquitin ligase complex. FBXL6 mediates phosphorylation-dependent ubiquitination, targeting specific proteins for degradation via the ubiquitin-proteasome pathway and thereby regulating diverse cellular processes, including cell cycle progression, apoptosis, DNA damage repair, and immune responses. FBXL6 also plays a specialized role in the quality control of cytosolic mitochondrial protein precursors. Dysregulated FBXL6 expression is associated with various cancers, including renal cell carcinoma, hepatocellular carcinoma, colorectal cancer, acute myeloid leukemia, and gliomas (notably glioblastoma), where its expression often correlates with tumor progression, poor prognosis, and altered drug sensitivity, making it both a putative therapeutic target and a prognostic biomarker.

Other names

F-box/LRR-repeat protein 6FBL6FBL6AF-box and leucine-rich repeat protein 6F-box protein FBL6PP14630F-box protein Fbl6

Drugs exhibiting enhanced efficacy in tumors with low FBXL6 expression (mechanism not fully defined; potentially due to altered regulation of protein degradation pathways)