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Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy.

Publication ,  Journal Article
Bodoor, K; Lontay, B; Safi, R; Weitzel, DH; Loiselle, D; Wei, Z; Lengyel, S; McDonnell, DP; Haystead, TA
Published in: J Biol Chem
September 9, 2011

During pregnancy, uterine smooth muscle (USM) coordinately adapts its contractile phenotype in order to accommodate the developing fetus and then prepare for delivery. Herein we show that SMTNL1 plays a major role in pregnancy to promote adaptive responses in USM and that this process is specifically mediated through interactions of SMTNL1 with the steroid hormone receptor PR-B. In vitro and in vivo SMTNL1 selectively binds PR and not other steroid hormone receptors. The physiological relationship between the two proteins was also established in global gene expression and transcriptional reporter studies in pregnant smtnl1(-/-) mice and by RNA interference in progesterone-sensitive cell lines. We show that the contraction-associated and progestin-sensitive genes (oxytocin receptor, connexin 43, and cyclooxygenase-2) and prolactins are down-regulated in pregnant smtnl1(-/-) mice. We suggest that SMTNL1 is a bifunctional co-regulator of PR-B signaling and thus provides a molecular mechanism whereby PR-B is targeted to alter gene expression patterns within USM cells to coordinately promote alterations in USM function during pregnancy.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

September 9, 2011

Volume

286

Issue

36

Start / End Page

31839 / 31851

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Receptors, Progesterone
  • Prolactin
  • Progestins
  • Pregnancy
  • Phosphoproteins
  • Myometrium
  • Muscle, Smooth
  • Muscle Proteins
  • Muscle Contraction
 

Citation

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Bodoor, K., Lontay, B., Safi, R., Weitzel, D. H., Loiselle, D., Wei, Z., … Haystead, T. A. (2011). Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy. J Biol Chem, 286(36), 31839–31851. https://doi.org/10.1074/jbc.M111.270397
Bodoor, Khaldon, Beata Lontay, Rachid Safi, Douglas H. Weitzel, David Loiselle, Zhengzheng Wei, Szabolcs Lengyel, Donald P. McDonnell, and Timothy A. Haystead. “Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy.J Biol Chem 286, no. 36 (September 9, 2011): 31839–51. https://doi.org/10.1074/jbc.M111.270397.
Bodoor K, Lontay B, Safi R, Weitzel DH, Loiselle D, Wei Z, et al. Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy. J Biol Chem. 2011 Sep 9;286(36):31839–51.
Bodoor, Khaldon, et al. “Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy.J Biol Chem, vol. 286, no. 36, Sept. 2011, pp. 31839–51. Pubmed, doi:10.1074/jbc.M111.270397.
Bodoor K, Lontay B, Safi R, Weitzel DH, Loiselle D, Wei Z, Lengyel S, McDonnell DP, Haystead TA. Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy. J Biol Chem. 2011 Sep 9;286(36):31839–31851.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

September 9, 2011

Volume

286

Issue

36

Start / End Page

31839 / 31851

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Receptors, Progesterone
  • Prolactin
  • Progestins
  • Pregnancy
  • Phosphoproteins
  • Myometrium
  • Muscle, Smooth
  • Muscle Proteins
  • Muscle Contraction