scholarly journals Combinatorial Expression of GATA4, Nkx2-5, and Serum Response Factor Directs Early Cardiac Gene Activity

2002 ◽  
Vol 277 (28) ◽  
pp. 25775-25782 ◽  
Author(s):  
Jorge L. Sepulveda ◽  
Spiros Vlahopoulos ◽  
Dinakar Iyer ◽  
Narasimhaswamy Belaguli ◽  
Robert J. Schwartz
Keyword(s):  
Serum Response Factor ◽  
Gene Activity ◽  
Response Factor ◽  
Cardiac Gene ◽  
Serum Response ◽  
Combinatorial Expression

scholarly journals Identification of a Novel Serum Response Factor Cofactor in Cardiac Gene Regulation

2004 ◽  
Vol 279 (53) ◽  
pp. 55626-55632 ◽  
Author(s):  
Xiaomin Zhang ◽  
Gohar Azhar ◽  
Ying Zhong ◽  
Jeanne Y. Wei
Keyword(s):  
Gene Regulation ◽  
Serum Response Factor ◽  
Response Factor ◽  
Cardiac Gene ◽  
Serum Response

scholarly journals Ternary Complex Factor-Serum Response Factor Complex-Regulated Gene Activity Is Required for Cellular Proliferation and Inhibition of Apoptotic Cell Death

2004 ◽  
Vol 24 (23) ◽  
pp. 10340-10351 ◽  
Author(s):  
Elaine R. Vickers ◽  
Aneta Kasza ◽  
Isil Aksan Kurnaz ◽  
Anne Seifert ◽  
Leo A. H. Zeef ◽  
...  
Keyword(s):  
Cell Death ◽  
Ternary Complex ◽  
Serum Response Factor ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Gene Activity ◽  
Immediate Early ◽  
Response Factor ◽  
Serum Response ◽  
Ternary Complex Factor

ABSTRACT Members of the ternary complex factor (TCF) subfamily of the ETS-domain transcription factors are activated through phosphorylation by mitogen-activated protein kinases (MAPKs) in response to a variety of mitogenic and stress stimuli. The TCFs bind and activate serum response elements (SREs) in the promoters of target genes in a ternary complex with a second transcription factor, serum response factor (SRF). The association of TCFs with SREs within immediate-early gene promoters is suggestive of a role for the ternary TCF-SRF complex in promoting cell cycle entry and proliferation in response to mitogenic signaling. Here we have investigated the downstream gene regulatory and phenotypic effects of inhibiting the activity of genes regulated by TCFs by expressing a dominantly acting repressive form of the TCF, Elk-1. Inhibition of ternary complex activity leads to the downregulation of several immediate-early genes. Furthermore, blocking TCF-mediated gene expression leads to growth arrest and triggers apoptosis. By using mutant Elk-1 alleles, we demonstrated that these effects are via an SRF-dependent mechanism. The antiapoptotic gene Mcl-1 is identified as a key target for the TCF-SRF complex in this system. Thus, our data confirm a role for TCF-SRF-regulated gene activity in regulating proliferation and provide further evidence to indicate a role in protecting cells from apoptotic cell death.

scholarly journals Activation of Cardiac Gene Expression by Myocardin, a Transcriptional Cofactor for Serum Response Factor

Cell ◽  
2001 ◽  
Vol 105 (7) ◽  
pp. 851-862 ◽  
Author(s):  
Da-Zhi Wang ◽  
Priscilla S. Chang ◽  
Zhigao Wang ◽  
Lillian Sutherland ◽  
James A. Richardson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Serum Response Factor ◽  
Response Factor ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Serum Response

scholarly journals Myocardin Sumoylation Transactivates Cardiogenic Genes in Pluripotent 10T1/2 Fibroblasts

2006 ◽  
Vol 27 (2) ◽  
pp. 622-632 ◽  
Author(s):  
Jun Wang ◽  
AnKang Li ◽  
ZhiGao Wang ◽  
XinHua Feng ◽  
Eric N. Olson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Posttranslational Modification ◽  
Serum Response Factor ◽  
Gene Activity ◽  
Response Factor ◽  
Dependent Manner ◽  
Sumoylation Site ◽  
Sumo Modification ◽  
Muscle Gene ◽  
Serum Response

ABSTRACT Myocardin, a serum response factor (SRF)-dependent cofactor, is a potent activator of smooth muscle gene activity but a poor activator of cardiogenic genes in pluripotent 10T1/2 fibroblasts. Posttranslational modification of GATA4, another myocardin cofactor, by sumoylation strongly activated cardiogenic gene activity. Here, we found that myocardin's activity was strongly enhanced by SUMO-1 via modification of a lysine residue primarily located at position 445 and that the conversion of this residue to arginine (K445R) impaired myocardin transactivation. PIAS1 was involved in governing myocardin activity via its E3 ligase activity that stimulated myocardin sumoylation on an atypical sumoylation site(s) and by its physical association with myocardin. Myocardin initiated the expression of cardiac muscle-specified genes, such as those encoding cardiac α-actin and α-myosin heavy chain, in an SRF-dependent manner in 10T1/2 fibroblasts, but only in the presence of coexpressed SUMO-1/PIAS1. Thus, SUMO modification acted as a molecular switch to promote myocardin's role in cardiogenic gene expression.

scholarly journals The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor

2021 ◽  
Vol 8 (5) ◽  
pp. 58
Author(s):  
Hazel Aberdeen ◽  
Kaela Battles ◽  
Ariana Taylor ◽  
Jeranae Garner-Donald ◽  
Ana Davis-Wilson ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Response Factor ◽  
Homeostatic Control ◽  
Older Americans ◽  
The Subject ◽  
Serum Response

The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hypoglycemia remain unclear and the subject of much debate. In this review, the molecular basis of the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular lesions and injury are discussed. Further, we review the potential role of the serum response factor (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins.

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