Regulation of the cell cycle at the G1-S transition by proteolysis of cyclin E and p27Kip1.
The transition from G1 phase to S phase of the mammalian cell cycle is controlled by many positive and negative regulators, among which cyclin E and p27Kip1, respectively, undergo the most marked changes in concentration at this transition. The abundance of both cyclin E and p27Kip1 is regulated predominantly by posttranslational mechanisms, in particular by proteolysis mediated by the ubiquitin-proteasome pathway. Cyclin E and p27Kip1 each bind to and undergo polyubiquitination by the same ubiquitin ligase, known as SCF(Skp2). The degradation of cyclin E and p27Kip1 is greatly impaired in Skp2-deficient mice, resulting in intracellular accumulation of these proteins. In this article, recent progress in characterization of the molecular mechanisms that control the proteolysis of cyclin E and p27Kip1 is reviewed.
Nakayama
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KI
Department of Molecular and Cellular Biology, Laboratory of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan. nakayak1@bioreg.kyushu-u.ac.jp
Hatakeyama
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Nakayama
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K
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D019927:Cyclin E / Q000378:metabolism* / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003546:Cysteine Endopeptidases / Q000378:metabolism; D016193:G1 Phase; D008025:Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010453:Peptide Synthases / Q000378:metabolism; D011123:Polyploidy; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D016196:S Phase; D044843:SKP Cullin F-Box Protein Ligases; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D019927:Cyclin E; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases; D010453:Peptide Synthases