title: Regulation of ribosomal protein S6 kinases by ubiquitination.
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.
authors.affiliation: Department of Structural and Molecular Biology, University College London, Gower Street, Darwin Building, London WC1E 6BT, United Kingdom.
authors.forename: Mong-Lien
authors.initials: ML
authors.lastname: Wang
authors.forename: Ganna
authors.initials: G
authors.lastname: Panasyuk
authors.forename: Jodie
authors.initials: J
authors.lastname: Gwalter
authors.forename: Ivan
authors.initials: I
authors.lastname: Nemazanyy
authors.forename: Tim
authors.initials: T
authors.lastname: Fenton
authors.forename: Valeriy
authors.initials: V
authors.lastname: Filonenko
authors.forename: Ivan
authors.initials: I
authors.lastname: Gout
mesh_terms: D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D019893:Ribosomal Protein S6 Kinases