Induction of homologue of Slimb ubiquitin ligase receptor by mitogen signaling

Vladimir S. Spiegelman, Weigang Tang, Andrew M. Chan, Makoto Igarashi, Stuart A. Aaronson, David A. Sassoon, Masaru Katoh, Thomas J. Slaga, Serge Y. Fuchs

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Homologue of Slimb (HOS) is the substrate-recognizing component of the SCFHOS-Roc1 E3 ubiquitin protein ligase. This ligase mediates ubiquitination of the inhibitor of NF-κB transcription factor (IκB). We have found that HOS is highly expressed in a number of human cancer cell lines. The rates of the HOS gene transcription as well as HOS mRNA and protein levels were up-regulated in cells treated with mitogens or transfected with the inducers of mitogen-activated protein kinase pathway. Conversely, mitogen withdrawal strikingly reduced HOS levels during differentiation of mouse myoblasts. Activators of mitogen-activated protein kinase accelerated IκBα degradation and increased NF-κB transcriptional activity. Inhibition of HOS function via expression of dominant negative HOS (HOSΔF) initiated mouse myoblast differentiation and prevented Ras-mediated acceleration of IκBα degradation as well as NF-κB trans-activation and transformation of NIH3T3 cells. These data link the induction of HOS in proliferating cells with mitogen-signaling-dependent inhibition of cell differentiation and promotion of cell transformation.

Original languageEnglish (US)
Pages (from-to)36624-36630
Number of pages7
JournalJournal of Biological Chemistry
Issue number39
StatePublished - Sep 27 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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