Steroid receptor coactivator-2 is a dual regulator of cardiac transcription factor function.
J Biol Chem
; 289(25): 17721-31, 2014 Jun 20.
Article
in En
| MEDLINE
| ID: mdl-24811170
ABSTRACT
We have previously demonstrated the potential role of steroid receptor coactivator-2 (SRC-2) as a co-regulator in the transcription of critical molecules modulating cardiac function and metabolism in normal and stressed hearts. The present study seeks to extend the previous information by demonstrating SRC-2 fulfills this role by serving as a critical coactivator for the transcription and activity of critical transcription factors known to control cardiac growth and metabolism as well as in their downstream signaling. This knowledge broadens our understanding of the mechanism by which SRC-2 acts in normal and stressed hearts and allows further investigation of the transcriptional modifications mediating different types and degrees of cardiac stress. Moreover, the genetic manipulation of SRC-2 in this study is specific for the heart and thereby eliminating potential indirect effects of SRC-2 deletion in other organs. We have shown that SRC-2 is critical to transcriptional control modulated by MEF2, GATA-4, and Tbx5, thereby enhancing gene expression associated with cardiac growth. Additionally, we describe SRC-2 as a novel regulator of PPARα expression, thus controlling critical steps in metabolic gene expression. We conclude that through regulation of cardiac transcription factor expression and activity, SRC-2 is a critical transcriptional regulator of genes important for cardiac growth, structure, and metabolism, three of the main pathways altered during the cardiac stress response.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Transcription Factors
/
Gene Expression Regulation
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Nuclear Receptor Coactivator 2
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Muscle Proteins
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Myocardium
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
2014
Type:
Article