Skip to main content

Peptidyl-prolyl isomerase 1 (Pin1) serves as a coactivator of steroid receptor by regulating the activity of phosphorylated steroid receptor coactivator 3 (SRC-3/AIB1).

Publication ,  Journal Article
Yi, P; Wu, R-C; Sandquist, J; Wong, J; Tsai, SY; Tsai, M-J; Means, AR; O'Malley, BW
Published in: Mol Cell Biol
November 2005

Steroid receptor coactivator 3 (SRC-3/AIB1) interacts with steroid receptors in a ligand-dependent manner to activate receptor-mediated transcription. A number of intracellular signaling pathways initiated by growth factors and hormones induce phosphorylation of SRC-3, regulating its function and contributing to its oncogenic potential. However, the range of mechanisms by which phosphorylation affects coactivator function remains largely undefined. We demonstrate here that peptidyl-prolyl isomerase 1 (Pin1), which catalyzes the isomerization of phosphorylated Ser/Thr-Pro peptide bonds to induce conformational changes of its target proteins, interacts selectively with phosphorylated SRC-3. In addition, Pin1 and SRC-3 activate nuclear-receptor-regulated transcription synergistically. Depletion of Pin1 by small interfering RNA (siRNA) reduces hormone-dependent transcription from both transfected reporters and an endogenous steroid receptor target gene. We present evidence that Pin1 modulates interactions between SRC-3 and CBP/p300. The interaction is enhanced in vitro and in vivo by Pin1 and diminished when cellular Pin1 is reduced by siRNA or in stable Pin1-depleted cell lines. Depletion of Pin1 in MCF-7 human breast cancer cells reduces the endogenous estrogen-dependent recruitment of p300 to the promoters of estrogen receptor-dependent genes. Pin1 overexpression enhanced SRC-3 cellular turnover, and depletion of Pin1 stabilized SRC-3. Our results suggest that Pin1 functions as a transcriptional coactivator of nuclear receptors by modulating SRC-3 coactivator protein-protein complex formation and ultimately by also promoting the turnover of the activated SRC-3 oncoprotein.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

November 2005

Volume

25

Issue

21

Start / End Page

9687 / 9699

Location

United States

Related Subject Headings

  • p300-CBP Transcription Factors
  • Transcriptional Activation
  • Trans-Activators
  • Receptors, Steroid
  • RNA, Small Interfering
  • Protein Binding
  • Phosphorylation
  • Peptidylprolyl Isomerase
  • Oncogene Proteins
  • Nuclear Receptor Coactivator 3
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yi, P., Wu, R.-C., Sandquist, J., Wong, J., Tsai, S. Y., Tsai, M.-J., … O’Malley, B. W. (2005). Peptidyl-prolyl isomerase 1 (Pin1) serves as a coactivator of steroid receptor by regulating the activity of phosphorylated steroid receptor coactivator 3 (SRC-3/AIB1). Mol Cell Biol, 25(21), 9687–9699. https://doi.org/10.1128/MCB.25.21.9687-9699.2005
Yi, Ping, Ray-Chang Wu, Joshua Sandquist, Jiemin Wong, Sophia Y. Tsai, Ming-Jer Tsai, Anthony R. Means, and Bert W. O’Malley. “Peptidyl-prolyl isomerase 1 (Pin1) serves as a coactivator of steroid receptor by regulating the activity of phosphorylated steroid receptor coactivator 3 (SRC-3/AIB1).Mol Cell Biol 25, no. 21 (November 2005): 9687–99. https://doi.org/10.1128/MCB.25.21.9687-9699.2005.
Yi, Ping, et al. “Peptidyl-prolyl isomerase 1 (Pin1) serves as a coactivator of steroid receptor by regulating the activity of phosphorylated steroid receptor coactivator 3 (SRC-3/AIB1).Mol Cell Biol, vol. 25, no. 21, Nov. 2005, pp. 9687–99. Pubmed, doi:10.1128/MCB.25.21.9687-9699.2005.
Yi P, Wu R-C, Sandquist J, Wong J, Tsai SY, Tsai M-J, Means AR, O’Malley BW. Peptidyl-prolyl isomerase 1 (Pin1) serves as a coactivator of steroid receptor by regulating the activity of phosphorylated steroid receptor coactivator 3 (SRC-3/AIB1). Mol Cell Biol. 2005 Nov;25(21):9687–9699.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

November 2005

Volume

25

Issue

21

Start / End Page

9687 / 9699

Location

United States

Related Subject Headings

  • p300-CBP Transcription Factors
  • Transcriptional Activation
  • Trans-Activators
  • Receptors, Steroid
  • RNA, Small Interfering
  • Protein Binding
  • Phosphorylation
  • Peptidylprolyl Isomerase
  • Oncogene Proteins
  • Nuclear Receptor Coactivator 3