Document Detail


Genetic inactivation of Cdk7 leads to cell cycle arrest and induces premature aging due to adult stem cell exhaustion.
MedLine Citation:
PMID:  22505032     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyclin-dependent kinase (Cdk)7, the catalytic subunit of the Cdk-activating kinase (CAK) complex has been implicated in the control of cell cycle progression and of RNA polymerase II (RNA pol II)-mediated transcription. Genetic inactivation of the Cdk7 locus revealed that whereas Cdk7 is completely dispensable for global transcription, is essential for the cell cycle via phosphorylation of Cdk1 and Cdk2. In vivo, Cdk7 is also indispensable for cell proliferation except during the initial stages of embryonic development. Interestingly, widespread elimination of Cdk7 in adult tissues with low proliferative indexes had no phenotypic consequences. However, ablation of conditional Cdk7 alleles in tissues with elevated cellular turnover led to the efficient repopulation of these tissues with Cdk7-expressing cells most likely derived from adult stem cells that may have escaped the inactivation of their targeted Cdk7 alleles. This process, a physiological attempt to maintain tissue homeostasis, led to the attrition of adult stem cell pools and to the appearance of age-related phenotypes, including telomere shortening and early death.
Authors:
Miguel Ganuza; Cristina Sáiz-Ladera; Marta Cañamero; Gonzalo Gómez; Ralph Schneider; María A Blasco; David Pisano; Jesús M Paramio; David Santamaría; Mariano Barbacid
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-13
Journal Detail:
Title:  The EMBO journal     Volume:  31     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-31     Completed Date:  2012-08-13     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2498-510     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / physiology*
Aging, Premature / genetics*
Animals
Cell Cycle Checkpoints / genetics,  physiology*
Cell Proliferation
Cyclin-Dependent Kinases / genetics,  physiology*
Embryonic Development / physiology
Female
Homeostasis / physiology
Mice
Telomere Shortening / physiology
Grant Support
ID/Acronym/Agency:
250297//European Research Council
Chemical
Reg. No./Substance:
EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.11.22/cyclin-dependent kinase 7, mouse
Comments/Corrections

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