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PMID:21771785

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Citation

Bodoor, K, Lontay, B, Safi, R, Weitzel, DH, Loiselle, D, Wei, Z, Lengyel, S, McDonnell, DP and Haystead, TA (2011) Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy. J. Biol. Chem. 286:31839-51

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.

Links

PubMed PMC3173130 Online version:10.1074/jbc.M111.270397

Keywords

Animals; Female; Gene Expression Profiling; Gene Expression Regulation/physiology; Mice; Muscle Contraction/physiology; Muscle Proteins/metabolism; Muscle Proteins/physiology; Muscle, Smooth/metabolism; Myometrium/metabolism; Myometrium/physiology; Phosphoproteins/metabolism; Phosphoproteins/physiology; Pregnancy; Progestins; Prolactin; Receptors, Progesterone/metabolism; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SMTL1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMTL1

GO:0016481: negative regulation of transcription

ECO:0000314:

P

Proven in Figure 7B

complete
CACAO 2113


See also

References

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