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Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation.

Publication ,  Journal Article
Su, S; Blackwelder, AJ; Grossman, G; Minges, JT; Yuan, L; Young, SL; Wilson, EM
Published in: J Biol Chem
October 5, 2012

Progesterone acting through the progesterone receptor (PR) and its coregulators prepares the human endometrium for receptivity to embryo implantation and maintains pregnancy. The menstrual cycle-dependent expression of melanoma antigen-A11 (MAGE-11) in the mid-secretory human endometrium suggested a novel function in human PR signaling. Here we show that MAGE-11 is an isoform-specific coregulator responsible for the greater transcriptional activity of human PR-B relative to PR-A. PR was recruited to progesterone response regions of progesterone-regulated FK506-binding protein 5 (FKBP5) immunophilin and small Ras family G protein cell growth inhibitor RASD1 genes. Expression of MAGE-11 lentivirus shRNA in human endometrial Ishikawa cells expressing PR-B showed that MAGE-11 is required for isoform-specific PR-B up-regulation of FKBP5. In contrast, MAGE-11 was not required for progesterone up-regulation of RASD1 in endometrial cells expressing the PR-A/B heterodimer. Target gene specificity of PR-B depended on the synergistic actions of MAGE-11 and p300 mediated by the unique PR-B NH(2)-terminal (110)LLXXVLXXLL(119) motif that interacts with the MAGE-11 F-box region in a phosphorylation- and ubiquitinylation-dependent manner. A progesterone-dependent mechanism is proposed in which MAGE-11 and p300 increase PR-B up-regulation of the FKBP5 gene. MAGE-11 down-regulates PR-B, similar to the effects of progesterone, and interacts with FKBP5 to stabilize a complex with PR-B. We conclude that the coregulator function of MAGE-11 extends to isoform-specific regulation of PR-B during the cyclic development of the human endometrium.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 5, 2012

Volume

287

Issue

41

Start / End Page

34809 / 34824

Location

United States

Related Subject Headings

  • ras Proteins
  • Up-Regulation
  • Transcriptional Activation
  • Tacrolimus Binding Proteins
  • Response Elements
  • Receptors, Progesterone
  • Protein Structure, Tertiary
  • Protein Multimerization
  • Pregnancy
  • Neoplasm Proteins
 

Citation

APA
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ICMJE
MLA
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Su, S., Blackwelder, A. J., Grossman, G., Minges, J. T., Yuan, L., Young, S. L., & Wilson, E. M. (2012). Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation. J Biol Chem, 287(41), 34809–34824. https://doi.org/10.1074/jbc.M112.372797
Su, Shifeng, Amanda J. Blackwelder, Gail Grossman, John T. Minges, Lingwen Yuan, Steven L. Young, and Elizabeth M. Wilson. “Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation.J Biol Chem 287, no. 41 (October 5, 2012): 34809–24. https://doi.org/10.1074/jbc.M112.372797.
Su S, Blackwelder AJ, Grossman G, Minges JT, Yuan L, Young SL, et al. Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation. J Biol Chem. 2012 Oct 5;287(41):34809–24.
Su, Shifeng, et al. “Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation.J Biol Chem, vol. 287, no. 41, Oct. 2012, pp. 34809–24. Pubmed, doi:10.1074/jbc.M112.372797.
Su S, Blackwelder AJ, Grossman G, Minges JT, Yuan L, Young SL, Wilson EM. Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation. J Biol Chem. 2012 Oct 5;287(41):34809–34824.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 5, 2012

Volume

287

Issue

41

Start / End Page

34809 / 34824

Location

United States

Related Subject Headings

  • ras Proteins
  • Up-Regulation
  • Transcriptional Activation
  • Tacrolimus Binding Proteins
  • Response Elements
  • Receptors, Progesterone
  • Protein Structure, Tertiary
  • Protein Multimerization
  • Pregnancy
  • Neoplasm Proteins