Regulation of ribosomal protein S6 kinases by ubiquitination

Wang, M-L, Panasyuk, G, Gwalter, J, Nemazanyy, I, Fenton, TR, Filonenko, V and Gout, I (2008) Regulation of ribosomal protein S6 kinases by ubiquitination. Biochemical and Biophysical Research Communications, 369 (2), 382-387. (doi:10.1016/j.bbrc.2008.02.032).

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.

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Contributors

Author: TR Fenton

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