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Bhatia, N, Herter, JR, Slaga, TJ, Fuchs, SY and Spiegelman, VS (2002) Mouse homologue of HOS (mHOS) is overexpressed in skin tumors and implicated in constitutive activation of NF-kappaB. Oncogene 21:1501-9
NF-kappaB transcription factor is activated upon ubiquitination and subsequent proteolysis of its inhibitor IkappaB. The phosphorylation-dependent ubiquitination is mediated by SCF E3 ubiquitin ligase. In this study, we identified a novel murine F-box/WD40 repeat-containing protein, mHOS (a homologue of HOS/betaTrCP2). mHOS efficiently binds Skp1 protein (a 'core' component of SCF ubiquitin ligase), and phosphorylated IkappaB(alpha). We found that mHOS associates with SCF-ROC1 E3 ubiquitin ligase activity. We have also observed that mHOS is overexpressed in chemically-induced mouse skin tumors, and its overexpression (but not accelerated IkappaB phosphorylation) coincides with the accelerated degradation of IkappaB in vivo. The role of mHOS in the constitutive activation of NF-kappaB in skin carcinogenesis is discussed.
Amino Acid Sequence; Animals; Carcinoma/chemically induced; Carcinoma/genetics; Carcinoma/metabolism; Carrier Proteins/biosynthesis; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Cycle Proteins/metabolism; Cell Line; DNA-Binding Proteins/metabolism; Female; GTP-Binding Proteins/genetics; I-kappa B Proteins; Immunohistochemistry; Mice; Molecular Sequence Data; NF-kappa B/immunology; NF-kappa B/metabolism; Neoplasm Proteins/biosynthesis; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Papilloma/chemically induced; Papilloma/genetics; Papilloma/metabolism; Peptide Synthases/metabolism; Phosphorylation; RNA, Neoplasm/biosynthesis; S-Phase Kinase-Associated Proteins; SKP Cullin F-Box Protein Ligases; Sequence Homology, Amino Acid; Skin Neoplasms/chemically induced; Skin Neoplasms/genetics; Skin Neoplasms/metabolism; Up-Regulation; beta-Transducin Repeat-Containing Proteins