Document Detail

Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7 cells.
MedLine Citation:
PMID:  16413017     Owner:  NLM     Status:  MEDLINE    
We have previously shown that the regulatory subunit of PKA, RIalpha, functions as a nuclear transport protein for the second subunit of the replication factor C complex, RFC40, and that this transport appears to be crucial for cell cycle progression from G1 to S phase. In this study, we found that N(6)-monobutyryl cAMP significantly up-regulates the expression of RFC40 mRNA by 1.8-fold and its endogenous protein by 2.3-fold with a subsequent increase in the RIalpha-RFC40 complex formation by 3.2-fold. Additionally, the nuclear to cytoplasmic ratio of RFC40 increased by 26% followed by a parallel increase in the percentage of S phase cells by 33%. However, there was reduction in the percentage of G1 cells by 16% and G2/M cells by 43% with a concurrent accumulation of cells in S phase. Interestingly, the higher percentage of S phase cells did not correlate with a parallel increase in DNA replication. Moreover, although cAMP did not affect the expression of the other RFC subunits, there was a significant decrease in the RFC40-37 complex formation by 81.3%, substantiating the decrease in DNA replication rate. Taken together, these findings suggest that cAMP functions as an upstream modulator that regulates the expression and nuclear translocation of RFC40.
Rakhee S Gupte; Valerie Sampson; Frank Traganos; Zbigniew Darzynkiewicz; Marietta Y W T Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-01-17
Journal Detail:
Title:  Experimental cell research     Volume:  312     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-20     Completed Date:  2006-05-16     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  796-806     Citation Subset:  IM    
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MeSH Terms
Active Transport, Cell Nucleus / physiology
Cell Line, Tumor
Cell Nucleus / drug effects,  metabolism*
Cyclic AMP / pharmacology,  physiology*
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
Cyclic AMP-Dependent Protein Kinases / drug effects,  metabolism
DNA Replication / drug effects
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects,  genetics
Replication Protein C / drug effects,  genetics*,  metabolism*
S Phase / drug effects
Transcription, Genetic / genetics
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0/PRKAR1A protein, human; 0/RFC2 protein, human; 0/Replication Protein C; E0399OZS9N/Cyclic AMP; EC AMP-Dependent Protein Kinases

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