Mouse homologue of HOS (mHOS) is overexpressed in skin tumors and implicated in constitutive activation of NF-kκB

Neehar Bhatia, Jason R. Herter, Thomas J. Slaga, Serge Y. Fuchs, Vladimir S. Spiegelman

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

NF-kκB transcription factor is activated upon ubiquitination and subsequent proteolysis of its inhibitor IκB. 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/βTrCP2). mHOS efficiently binds Skp1 protein (a 'core' component of SCF ubiquitin ligase), and phosphorylated IκBα. 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 IκB phosphorylation) coincides with the accelerated degradation of IκB in vivo. The role of mHOS in the constitutive activation of NF-κB in skin carcinogenesis is discussed.

Original languageEnglish (US)
Pages (from-to)1501-1509
Number of pages9
JournalOncogene
Volume21
Issue number10
DOIs
StatePublished - Feb 28 2002

Keywords

  • F-box
  • HOS
  • NF-κB
  • Skin carcinogenesis
  • Ubiquitin ligase
  • βTrCP

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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