Document Detail

Coordinated changes in cell cycle machinery occur during keratinocyte terminal differentiation.
MedLine Citation:
PMID:  9927196     Owner:  NLM     Status:  MEDLINE    
Differentiation of cells is typically marked by a cessation of proliferation with a concurrent entrance into a distinct metabolic state marked by tissue specific gene expression. The mechanism by which the cell exits the cell cycle in this process is poorly understood. To determine the potential roles of the cell cycle machinery in the regulation of the terminal differentiation process of epidermal cells, we selected a well characterized in vitro model in which primary mouse keratinocytes are induced to differentiate in response to a raised calcium ion concentration in the medium. The withdrawal from the cell cycle correlates very well with a number of changes in the cell cycle machinery. Changes in the phosphorylation status of the Rb family of proteins occurs coordinately with an increased association of p21, p27 and p57 with cdk2. Furthermore, we find that inhibition of cdk2 activity is not sufficient to elicit changes that occur during keratinocyte differentiation. Finally, the previously described v-Ha-ras block of keratinocyte differentiation correlates with altered regulation of both cyclin D1 and cdk2 suggesting that these genes may play a role in the Ha-ras transformation of a keratinocyte.
L A Martinez; Y Chen; S M Fischer; C J Conti
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  18     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-16     Completed Date:  1999-02-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  397-406     Citation Subset:  IM    
The University of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville, USA.
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MeSH Terms
Cell Cycle*
Cell Differentiation*
Cells, Cultured
Cyclin-Dependent Kinases / antagonists & inhibitors,  metabolism
Cyclins / metabolism
Keratinocytes / cytology*,  enzymology,  metabolism
Oncogene Protein p21(ras) / metabolism
Grant Support
Reg. No./Substance:
0/Cyclins; EC Kinases; EC Protein p21(ras)

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