PMID- 15601848 OWN - NLM STAT- MEDLINE DCOM- 20050118 LR - 20181201 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 25 IP - 1 DP - 2005 Jan TI - Cyclin-dependent kinase activity is required for progesterone receptor function: novel role for cyclin A/Cdk2 as a progesterone receptor coactivator. PG - 264-77 AB - Our studies examining the role of the cell cycle-regulated kinase cyclin A/Cdk2 in progesterone receptor (PR) action have demonstrated that cyclin-dependent kinase activity is required for PR function and that cyclin A/Cdk2 functions as a PR coactivator. Although Cdk2 can phosphorylate PR, elimination of these phosphorylation sites has little effect on the ability of cyclin A/Cdk2 to stimulate PR activity. PR interacts with cyclin A and recruits cyclin A/Cdk2 to progestin-responsive promoters, stimulating transcription. Inhibition of Cdk2 activity abolishes progesterone-dependent activation of PR target genes in part through inhibition of PR-dependent recruitment of steroid receptor coactivator 1 (SRC-1) and subsequent histone H4 acetylation at the target promoter. In vitro studies revealed that the interaction between SRC-1 and PR is dependent upon phosphorylation of SRC-1. This heretofore-unknown mechanism provides a potential means for integrating the regulation of PR activity with cell cycle progression. Moreover, the ability of PR to recruit cyclin A/Cdk2 to target promoters provides locally elevated levels of kinase, which can preferentially facilitate phosphorylation-dependent interactions and enzymatic activities of coactivators at the target promoter. FAU - Narayanan, Ramesh AU - Narayanan R AD - Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. FAU - Adigun, Abayomi A AU - Adigun AA FAU - Edwards, Dean P AU - Edwards DP FAU - Weigel, Nancy L AU - Weigel NL LA - eng GR - R01 CA057539/CA/NCI NIH HHS/United States GR - T32 HD007165/HD/NICHD NIH HHS/United States GR - R01 CA 57539/CA/NCI NIH HHS/United States GR - T32 HD 07165/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Cyclin A) RN - 0 (Histones) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Purines) RN - 0 (Receptors, Progesterone) RN - 0 (Transcription Factors) RN - 0ES1C2KQ94 (Roscovitine) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.5.1.18 (Glutathione Transferase) RN - EC 2.7.11.22 (CDC2-CDC28 Kinases) RN - EC 2.7.11.22 (CDK2 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 2) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) RN - K3Z4F929H6 (Lysine) SB - IM MH - Acetylation MH - Animals MH - Blotting, Western MH - CDC2-CDC28 Kinases/*metabolism MH - COS Cells MH - Cell Cycle MH - Cell Line MH - Chromatin Immunoprecipitation MH - Cyclin A/*metabolism MH - Cyclin-Dependent Kinase 2 MH - Cyclin-Dependent Kinases/*metabolism MH - Genes, Reporter MH - Genetic Vectors MH - Glutathione Transferase/metabolism MH - HeLa Cells MH - Histone Acetyltransferases MH - Histones/metabolism MH - Humans MH - Immunoprecipitation MH - Lysine/chemistry MH - Models, Genetic MH - Nuclear Receptor Coactivator 1 MH - Phosphorylation MH - Plasmids/metabolism MH - Promoter Regions, Genetic MH - Protein Binding MH - Protein Biosynthesis MH - Protein Kinase Inhibitors/pharmacology MH - Purines/pharmacology MH - Receptors, Progesterone/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Roscovitine MH - Transcription Factors/metabolism MH - Transcription, Genetic MH - Transcriptional Activation MH - Transfection MH - Two-Hybrid System Techniques PMC - PMC538783 EDAT- 2004/12/17 09:00 MHDA- 2005/01/19 09:00 PMCR- 2005/01/01 CRDT- 2004/12/17 09:00 PHST- 2004/12/17 09:00 [pubmed] PHST- 2005/01/19 09:00 [medline] PHST- 2004/12/17 09:00 [entrez] PHST- 2005/01/01 00:00 [pmc-release] AID - 25/1/264 [pii] AID - 1330-04 [pii] AID - 10.1128/MCB.25.1.264-277.2005 [doi] PST - ppublish SO - Mol Cell Biol. 2005 Jan;25(1):264-77. doi: 10.1128/MCB.25.1.264-277.2005.