| Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7 cells. | |
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MedLine Citation:
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PMID: 16413017 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Rakhee S Gupte; Valerie Sampson; Frank Traganos; Zbigniew Darzynkiewicz; Marietta Y W T Lee |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-01-17 |
Journal Detail:
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Title: Experimental cell research Volume: 312 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-03-20 Completed Date: 2006-05-16 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 796-806 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus
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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 Humans Replication Protein C / drug effects, genetics*, metabolism* S Phase / drug effects Transcription, Genetic / genetics Tumor Cells, Cultured Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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GM31973/GM/NIGMS NIH HHS; R01 CA028704-27/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0/PRKAR1A protein, human; 0/RFC2 protein, human; 0/Replication Protein C; 60-92-4/Cyclic AMP; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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