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PMID:11896578

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Citation

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

Abstract

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.

Links

PubMed Online version:10.1038/sj.onc.1205311

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FBW1B

contributes_to

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FBW1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Z1E3

F

Seeded From UniProt

complete

MOUSE:FBW1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WTX5

F

Seeded From UniProt

complete

MOUSE:FBW1B

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FBW1B

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBW1B

involved_in

GO:0031146: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FBW1B

part_of

GO:0019005: SCF ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBW1B

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FBW1B

involved_in

GO:1901223: negative regulation of NIK/NF-kappaB signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SKP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5SRY7

F

Seeded From UniProt

complete

MOUSE:IKBA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5SRY7

F

Seeded From UniProt

complete


See also

References

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