Cyclin dependent kinase 2 and the regulation of human progesterone receptor activity

Nicole L. Moore, Ramesh Narayanan, Nancy L. Weigel

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The function of the S phase kinase cyclin A/Cdk2 in maintaining and regulating cell cycle kinetics is well established. However an alternative role in the regulation of progesterone receptor (PR) signaling is emerging. PR and its coactivators are phosphoproteins. Cyclin A/Cdk2 phosphorylates several of the PR phosphorylation sites in vitro and there is evidence that it participates in PR phosphorylation in vivo. Cyclin A/Cdk2 also functions as a PR coactivator. Overexpression increases PR transcriptional activity independent of PR phosphorylation. In the presence of hormone, cyclin A/Cdk2 is recruited to PR bound to DNA of target genes. Inhibition of Cdk activity prevents recruitment of the p160 coactivator steroid receptor coactivator-1 (SRC-1), suggesting that Cdk2 phosphorylates SRC-1. Consistent with this finding, phosphatase treatment of SRC-1 reduces its ability to interact with PR in vitro. Moreover, PR transcriptional activity is highest in S phase where cyclin A is expressed. In G1, PR activity is reduced and the capacity to recruit SRC-1 to a progestin responsive promoter is diminished. Future studies will focus on the importance of cyclin A/Cdk2 phosphorylation of other components of the PR transcription complex, such as the p160 coactivator SRC-1, and the specific role of Cdk2 target sites in the regulation of PR activity.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalSteroids
Volume72
Issue number2
DOIs
StatePublished - Feb 1 2007

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Cyclin-Dependent Kinase 2
Progesterone Receptors
Nuclear Receptor Coactivator 1
Cyclin A
Phosphorylation
S Phase
human CDK2 protein
Personnel Selection
Phosphoproteins
Progestins
Transcription
Phosphoric Monoester Hydrolases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Cyclin dependent kinase 2 and the regulation of human progesterone receptor activity. / Moore, Nicole L.; Narayanan, Ramesh; Weigel, Nancy L.

In: Steroids, Vol. 72, No. 2, 01.02.2007, p. 202-209.

Research output: Contribution to journalArticle

Moore, Nicole L. ; Narayanan, Ramesh ; Weigel, Nancy L. / Cyclin dependent kinase 2 and the regulation of human progesterone receptor activity. In: Steroids. 2007 ; Vol. 72, No. 2. pp. 202-209.
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