The brain-specific activator p35 allows Cdk5 to escape inhibition by p27(Kip1) in neurons Journal Article
| Authors: | Lee, M. H.; Nikolic, M.; Baptista, C. A.; Lai, E.; Tsai, L. H.; Massagué, J. |
| Article Title: | The brain-specific activator p35 allows Cdk5 to escape inhibition by p27(Kip1) in neurons |
| 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 Cdk2 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. |
| Keywords: | immunohistochemistry; controlled study; nonhuman; mitosis; animals; cell cycle proteins; mice; animal tissue; cell cycle; enzyme inhibition; embryo; protein protein interaction; nerve tissue proteins; neurons; enzyme activation; brain; protein-serine-threonine kinases; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; rat; pregnancy; rats; rats, sprague-dawley; cyclin-dependent kinases; cyclin dependent kinase; enzyme binding; nervous system development; neuroblast; microtubule-associated proteins; brain cell; female; priority journal; article; cyclin-dependent kinase 5 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 93 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1996-04-16 |
| Start Page: | 3259 |
| End Page: | 3263 |
| Language: | English |
| PUBMED: | 8622924 |
| PROVIDER: | scopus |
| PMCID: | PMC39593 |
| DOI: | 10.1073/pnas.93.8.3259 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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