Bone morphogenetic protein signaling modulates myocardin transactivation of cardiac genes.

Abstract:

:Bone morphogenetic proteins (BMPs) play important roles in cardiovascular development. However, how BMP-signaling pathways regulate cardiac gene expression is less clear. We have previously identified myocardin as a cardiac and smooth muscle-specific transcriptional cofactor for serum response factor (SRF). Myocardin potently activates target gene expression by tethering with SRF bound to SRF-responsive elements, the CArG box. Here, we show that Smad1, an effector of the BMP-signaling pathway, synergistically activates myocardin-dependent cardiac gene expression. Interestingly, the CArG box is necessary and sufficient to mediate such synergy, whereas no obvious Smad-binding element appears to be involved. Consistent with their functional interaction, we find that myocardin and Smad1 proteins interact directly. Furthermore, myocardin protein levels were dramatically increased by BMP-2 treatment in cardiomyocytes. These findings suggest myocardin participates in a BMP signaling-dependent cardiac gene transcriptional program.

journal_name

Circ Res

journal_title

Circulation research

authors

Callis TE,Cao D,Wang DZ

doi

10.1161/01.RES.0000190670.92879.7d

subject

Has Abstract

pub_date

2005-11-11 00:00:00

pages

992-1000

issue

10

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000190670.92879.7d

journal_volume

97

pub_type

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