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Biochem Biophys Res Commun. 2008 May 2;369(2):382-7. doi: 10.1016/j.bbrc.2008.02.032. Epub 2008 Feb 15.

Regulation of ribosomal protein S6 kinases by ubiquitination.

Author information

1
Department of Structural and Molecular Biology, University College London, Gower Street, Darwin Building, London WC1E 6BT, United Kingdom.

Abstract

Ribosomal protein S6 kinase (S6K) is a key player in the regulation of cell growth and energy metabolism via the mTOR and PI3K signalling pathways. The activity and subcellular localization of S6K are regulated by multiple S/T phosphorylations in response to diverse extracellular stimuli. Downregulation of S6K signalling occurs through the action of S/T phosphatases (PP2A and PP1) and tumor suppressors (TSC1/2 and PTEN). We report here that, in addition to phosphorylation, S6Ks are ubiquitinated in cells. The pattern of ubiquitination and the effect of proteasomal inhibitors on the steady-state level of transiently overexpressed and endogenous S6Ks point to proteasome-mediated degradation of ubiquitinated S6Ks. Furthermore, we found that the site(s) of ubiquitination are located in the kinase domain and that the N- and C-terminal regulatory regions modulate the efficiency of S6K ubiquitination. This study suggests that S6K signalling also could be regulated through the proteasome-mediated turnover of S6Ks.

PMID:
18280803
DOI:
10.1016/j.bbrc.2008.02.032
[Indexed for MEDLINE]

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