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Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8561-6. Epub 2005 Jun 6.

Gene expression patterns define key transcriptional events in cell-cycle regulation by cAMP and protein kinase A.

Author information

1
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141, USA.

Abstract

Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP), a PKA-selective cAMP analog, alters the expression of approximately 4,500 of approximately 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPT-cAMP. Changes in mRNA and protein expression of several cell-cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2 h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.

PMID:
15939874
PMCID:
PMC1150853
DOI:
10.1073/pnas.0503363102
[Indexed for MEDLINE]
Free PMC Article

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