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Title: Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7 cells

Journal Article · · Experimental Cell Research
 [1];  [1];  [2];  [2]
  1. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595 (United States)
  2. Brander Cancer Research Institute, New York Medical College, Valhalla, NY 10595 (United States)

We have previously shown that the regulatory subunit of PKA, RI{alpha}, 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 {sup 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 RI{alpha}-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.

OSTI ID:
20775347
Journal Information:
Experimental Cell Research, Vol. 312, Issue 6; Other Information: DOI: 10.1016/j.yexcr.2005.11.033; PII: S0014-4827(05)00565-3; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
Country of Publication:
United States
Language:
English