Cyclin-dependent kinase activity is required for progesterone receptor function

Novel role for cyclin A/Cdk2 as a progesterone receptor coactivator

Ramesh Narayanan, Abayomi A. Adigun, Dean P. Edwards, Nancy L. Weigel

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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 coactivaior. 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.

Original languageEnglish (US)
Pages (from-to)264-277
Number of pages14
JournalMolecular and cellular biology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2005

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Cyclin A
Cyclin-Dependent Kinases
Progesterone Receptors
Nuclear Receptor Coactivator 1
Phosphorylation
Cell Cycle
Phosphotransferases
Progestins
Acetylation
Histones
Progesterone

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Cyclin-dependent kinase activity is required for progesterone receptor function : Novel role for cyclin A/Cdk2 as a progesterone receptor coactivator. / Narayanan, Ramesh; Adigun, Abayomi A.; Edwards, Dean P.; Weigel, Nancy L.

In: Molecular and cellular biology, Vol. 25, No. 1, 01.01.2005, p. 264-277.

Research output: Contribution to journalArticle

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