The ubiquitination of ribosomal S6 kinases is independent from the mitogen-induced phosphorylation/activation of the kinase.
Ribosomal protein S6 kinase plays a critical role in the regulation of cell growth and energy metabolism. S6K belongs to the AGC family of serine/threonine kinases and is a downstream effector of the mTOR and PI3K signalling pathways. The activity and subcellular localisation of S6K are tightly controlled by phosphorylation/dephosphorylation events. We have recently demonstrated that steady-state levels of S6K isoforms, S6K1 and S6K2, are regulated by ubiquitination-mediated proteasomal degradation. In this study, we report for the first time that the ubiquitination status of S6K isoforms is coordinated by signalling pathways induced by mitogenic stimuli and extracellular stresses. The induction of signal transduction by serum and growth factors significantly increases the level of S6K ubiquitination, while the treatment of cells with UV and staurosporine has the opposite effect. Furthermore, we found that the phosphorylation/activation of S6Ks does not correlate directly with the induction of their ubiquitination in response to diverse cellular stimuli. This study suggests that the ubiquitination and subsequent proteasomal degradation of S6K are controlled by signalling pathways, which could possibly facilitate their association with the components of the ubiquitination machinery.
Gwalter
J
J
Research Department of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Wang
M-L
ML
Gout
I
I
D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes; D010766:Phosphorylation / Q000528:radiation effects; D020033:Protein Isoforms; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D025801:Ubiquitin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000528:radiation effects; D014466:Ultraviolet Rays
D007527:Isoenzymes; D020033:Protein Isoforms; D025801:Ubiquitin; D019893:Ribosomal Protein S6 Kinases; D019311:Staurosporine