Fbxw7 Rabbit Polyclonal Antibody (ER1706-78)

UNIPROT #

Q969H0

PROTEIN NAME

FBXW7

SYNONYMS

AGO antibody;Archipelago antibody;Archipelago homolog antibody;Archipelago, Drosophila, homolog of antibody;CDC4 antibody;CDC4, S.cerevisiae, homolog of antibody;DKFZp686F23254 antibody;F box and WD 40 domain protein 7 (archipelago homolog, Drosophila) antibody;F box and WD 40 domain protein 7 antibody;F box and WD repeat domain containing 7 antibody;F box protein FBW7 antibody;F box protein FBX30 antibody;F box protein SEL 10 antibody;F box protein SEL10 antibody;F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase antibody;F-box and WD-40 domain-containing protein 7 antibody;F-box protein FBX30 antibody;F-box/WD repeat-containing protein 7 antibody;FBW6 antibody;FBW7 antibody;FBX30 antibody;FBXO30 antibody;FBXW6 antibody;FBXW7 antibody;FBXW7_HUMAN antibody;FLJ16457 antibody;hAgo antibody;hCdc4 antibody;Homolog of C elegans sel 10 antibody;Homolog of C.elegans sel10 antibody;SEL 10 antibody;SEL-10 antibody;SEL10 antibody

TISSUE SPECIFICITY

Isoform 1 is widely expressed. Isoform 3 is expressed in brain.

POST-TRANSLATIONAL MODIFICATION

Phosphorylation at Thr-205 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation.; Ubiquitinated: autoubiquitinates following phosphorylation at Thr-205 and subsequent interaction with PIN1. Ubiquitination leads to its proteasomal degradation.

SUBCELLULAR LOCATION

Cytoplasm. Nucleus.

FUNCTION

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers [e.g., cholangiocarcinoma (35%), T-ALL (31%), endometrial carcinoma (16%), colorectal carcinoma (16%), bladder cancer (10%), gastric carcinoma (6%), lung squamous cell carcinoma (5%), etc.]. These findings implicate the gene's potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and multiple myeloma. One possibility is that FBXW7 substrate stabilization is detrimental in these neoplasms. For example, the FBXW7 substrate C/EBPα suppresses AML[8] and multiple myelomas require constitutive NF-κB signaling; therefore, disruption of FBXW7-mediated ubiquitylation of IκBd in these tumors results in cell death.