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PMID: 9784491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development.

Genes & development ·Vol. 12 ·No. 20 ·1998-10-15 ·Pages 3162-7

Zhang P, Wong C, DePinho RA, Harper JW, Elledge SJ

Abstract

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.

MeSH Terms
Animals Cell Cycle Cell Cycle Proteins Cell Differentiation Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinase Inhibitor p57 Cyclin-Dependent Kinases/antagonists & inhibitors Embryo, Mammalian Enzyme Inhibitors/pharmacology Lens, Crystalline/cytology,embryology Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Microtubule-Associated Proteins/physiology Nuclear Proteins/physiology Placenta/cytology,embryology Tumor Suppressor Proteins
Chemicals
Cdkn1b protein, mouse Cdkn1c protein, mouse Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p57 Enzyme Inhibitors Microtubule-Associated Proteins Nuclear Proteins Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhang P
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461 USA.
Wong C
DePinho R A
Harper J W
Elledge S J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.20.3162
Published
1998-10-15
Pages
3162-7
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317217
Subset
IM
Grants
NEI NIH HHS · EY09300 · United States
NEI NIH HHS · EY11267 · United States
External Links
PubMed source DOI: 10.1101/gad.12.20.3162 PMC Full Text View journal details
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