FBXW8
Description
The FBXW8 (F-box and WD repeat domain containing 8) is a protein-coding gene located on chromosome 12.
FBXW8 (F-box/WD repeat-containing protein 8) is a protein encoded by the FBXW8 gene in humans. It belongs to the F-box protein family, characterized by an F-box motif and a WD-40 domain. FBXW8 is part of the SCF (SKP1-cullin-F-box) ubiquitin-protein ligase complex, which plays a crucial role in phosphorylation-dependent ubiquitination. This protein is classified as an Fbw, as it contains both an F-box motif and a WD-40 domain. Alternative splicing of the FBXW8 gene leads to different isoforms of the protein.
FBXW8 is a substrate-recognition component of the Cul7-RING ubiquitin-protein ligase complex, which plays a key role in the ubiquitination and subsequent degradation of target proteins. This complex is involved in various cellular processes, including:
- Golgi morphogenesis and dendrite patterning in the brain: FBXW8, as part of the Cul7-RING(FBXW8) complex, mediates the ubiquitination and degradation of GORASP1, a protein essential for these processes.
- Regulation of insulin signaling: FBXW8 mediates the ubiquitination and degradation of IRS1, an important component of insulin signaling, in a mTOR-dependent manner. This process involves the recognition and binding of IRS1 by the Cul7-RING(FBXW8) complex after IRS1 has been phosphorylated by S6 kinase.
- Cell proliferation and differentiation: FBXW8 is involved in the ubiquitination and degradation of MAP4K1/HPK1, a protein that regulates cell proliferation and differentiation. The Cul7-RING(FBXW8) complex recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation.
- Other cellular functions: FBXW8 is an associated component of the 3M complex, suggesting its involvement in mediating some of the 3M complex functions.
FBXW8 is also known as FBW6, FBW8, FBX29, FBXO29, FBXW6.
