Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development.
Cell cycle exit is required for terminal differentiation of many cell types. The retinoblastoma protein Rb has been implicated both in cell cycle exit and differentiation in several tissues. Rb is negatively regulated by cyclin-dependent kinases (Cdks). The main effectors that down-regulate Cdk activity to activate Rb are not known in the lens or other tissues. In this study, using multiple mutant mice, we show that the Cdk inhibitors p27(KIP1) and p57(KIP2) function redundantly to control cell cycle exit and differentiation of lens fiber cells and placental trophoblasts. These studies demonstrate that p27(KIP1) and p57(KIP2) are critical terminal effectors of signal transduction pathways that control cell differentiation.
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461 USA.
P
P
Zhang
C
C
Wong
R A
RA
DePinho
J W
JW
Harper
S J
SJ
Elledge
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010920:Placenta / Q000166:cytology / Q000196:embryology; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; C493965:Cdkn1c protein, mouse; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases