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

Khaldon Bodoor, Beata Lontay, Rachid Safi, Douglas H. Weitzel, David Loiselle, Zhengzheng Wei, Szabolcs Lengyel, Donald P. McDonnell, Timothy A. Haystead

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13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)31839-31851
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number36
DOIs
Publication statusPublished - Sep 9 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bodoor, K., Lontay, B., Safi, R., Weitzel, D. H., Loiselle, D., Wei, Z., Lengyel, S., McDonnell, D. P., & Haystead, T. A. (2011). Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy. Journal of Biological Chemistry, 286(36), 31839-31851. https://doi.org/10.1074/jbc.M111.270397