Regulation of p70s6k/p85s6k and its role in the cell cycle.
Two to three-fold increases in the rate of protein synthesis are required both to enter the G1 phase of the cell cycle from G0 and to proceed to S phase in response to growth factors and mitogens. This increase is in part regulated via multiple phosphorylation of the 40S ribosomal protein S6 by the mitogen-stimulated p70s6k/p85s6k. At the protein synthesis level this event appears to be involved in specifically increasing the efficiency of translation of a family of essential mRNAs containing a polypyrimidine tract at their 5' transcriptional start site. The activation of p70s6k/p85s6k and maintenance of its activity throughout G1 is controlled via multiple phosphorylation events mediated by a complex signalling network acting on distinct sets of phosphorylation sites.
Pearson
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Friedrich Miescher Institute, Basel, Switzerland.
Thomas
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D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011090:Polyenes / Q000494:pharmacology; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology; D038601:Ribosomal Protein S6; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D012269:Ribosomal Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D011090:Polyenes; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D000242:Cyclic AMP; D017479:Receptors, Platelet-Derived Growth Factor; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus