Using kinetic studies to uncover new Rb functions in inhibiting cell cycle progression.
A well-established biological activity of the tumor suppressor Rb is blocking G1/S cell cycle progression when reintroduced into cultured Rb-deficient tumor cells. The best understood molecular mechanism underlying this function is that Rb binds the transcription factor E2F to repress expression of S phase genes such as cyclins E and A. A recent kinetic study of this model further revealed that Rb represses Skp2 to stabilize p27, which inhibits the kinase activity associated with cyclins E and A before the decline in their protein levels, to arrest the cell cycle. This p27-stabilizing function of Rb is retained in a clinical partial penetrance Rb mutant that is biochemically inactive for E2F repression, suggesting a mechanism for Rb-mediated inhibition of tumor progression.
Ji
Peng
P
Department of Developmental and Molecular Biology, The Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Zhu
Liang
L
D000818:Animals; D002453:Cell Cycle; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D018450:Disease Progression; D050684:E2F Transcription Factors / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology*; D016196:S Phase; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism
D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA