FBXW7 (F8B6C) Rabbit Monoclonal Antibody #49367

F-box and WD repeat-containing protein 7 (FBXW7) is a tumor suppressor protein that acts as the substrate-recognition component of the SCF (Skp1/CUL1/F-box) E3 ubiquitin ligase complex (1,2). Substrate recognition is mediated via interactions between WD40 repeat domains in FBXW7 and Cdc4 phosphodegron (CPD) motifs in the substrate, which are frequently phosphorylated by glycogen synthase kinase-3 (3,4). The primary function of FBXW7 is to facilitate ubiquitination and proteasomal degradation of several key proto-oncoprotein substrates, including c-Myc, cyclin E, Notch1, and Mcl-1, to regulate cell growth, cell cycle, differentiation, and apoptosis (5,6). Three distinct FBXW7 isoforms (alpha, beta, and gamma) localize to different parts of the cell (nucleus, cytoplasm, and nucleolus, respectively), allowing FBXW7 to monitor oncoproteins throughout the cellular environment (7).

FBXW7 is one of the most frequently mutated genes in human cancers, with most mutations occurring within the WD40 domain; therefore, preventing FBXW7 from binding to target substrates and driving hyperproliferation and genomic instability (8-10). FBXW7 mutations are found in over 30% of T-cell acute lymphoblastic leukemia cases (11), and loss of FBXW7 is correlated with poor clinical outcome in colorectal cancer (12). Studies have also shown that FBXW7 inactivation can promote drug resistance through several mechanisms such as apoptosis evasion (via stabilization of Mcl-1) or epithelial-mesenchymal transition (via stabilization of ZEB2) (13,14). Additionally, because FBXW7 regulates SREBP-1 and c-Myc, its dysregulation may also be linked to disorders involving lipid and glucose metabolism (15).