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Vol. 12, No. 20, pp. 3162-3167, October 15, 1998
1 Howard Hughes Medical Institute,
2 Verna & Marrs McLean Department of Biochemistry,
3 Department of
Molecular and Human Genetics,
4 Department of
Microbiology and Immunology, Albert Einstein College of Medicine,
Bronx, New York 10461 USA
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 p27KIP1 and
p57KIP2 function redundantly to control cell cycle
exit and differentiation of lens fiber cells and placental
trophoblasts. These studies demonstrate that p27KIP1
and p57KIP2 are critical terminal effectors of signal
transduction pathways that control cell differentiation.
[Key Words: Cdk inhibitors; cell differentation; tissue growth; cell development]
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