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PMID: 8622924 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.

The brain-specific activator p35 allows Cdk5 to escape inhibition by p27Kip1 in neurons.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 8 ·1996-04-16 ·Pages 3259-63

Lee MH, Nikolic M, Baptista CA, Lai E, Tsai LH, Massagué J

Abstract

Cell cycle withdrawal in postmitotic cells involves cyclin-dependent kinase (Cdk) inhibitors that repress cell cycle Cdk activity. During mouse neurogenesis, cortical postmitotic neurons are shown here to accumulate high levels of the p27 Cdk inhibitor compared with their progenitor neuroblasts. Elevated p27 levels in staged embryo brain extracts correlate with p27 binding to Cdk2, and Cdk inactivation. Yet, Cdk5, which is associated with the noncyclin activator p35 in neurons, remains active in the presence of high p27 levels. Both in vitro and in vivo, p27 and related inhibitors can recognize a cyclin D-Cdk5 complex but not a p35-Cdk5 complex. The results indicate that the choice of activator determines the susceptibility of Cdk5 to p27 and related Cdk inhibitors, and thus its ability to act in postmitotic cells.

MeSH Terms
Animals Brain/embryology,metabolism Cell Cycle Cell Cycle Proteins Cyclin-Dependent Kinase 5 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases Female Immunohistochemistry In Vitro Techniques Mice Microtubule-Associated Proteins/metabolism Nerve Tissue Proteins/metabolism Neurons/cytology,metabolism Pregnancy Protein Serine-Threonine Kinases/metabolism Rats Rats, Sprague-Dawley Tumor Suppressor Proteins
Chemicals
Cdkn1b protein, mouse Cdkn1b protein, rat Cell Cycle Proteins Microtubule-Associated Proteins Nerve Tissue Proteins Tumor Suppressor Proteins neuronal Cdk5 activator (p25-p35) Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinase 5 Protein Serine-Threonine Kinases Cdk5 protein, mouse Cdk5 protein, rat Cyclin-Dependent Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lee M H
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Nikolic M
Baptista C A
Lai E
Tsai L H
Massagué J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.8.3259
Published
1996-04-16
Pages
3259-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC39593
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.8.3259 PMC Full Text View journal details
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