TY - JOUR
T1 - Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts
AU - Wang, Jun
AU - Li, AnKang
AU - Wang, ZhiGao
AU - Feng, XinHua
AU - Olson, Eric N.
AU - Schwartz, Robert J.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846182262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846182262&partnerID=8YFLogxK
U2 - 10.1128/MCB.01160-06
DO - 10.1128/MCB.01160-06
M3 - Article
C2 - 17101795
AN - SCOPUS:33846182262
SN - 0270-7306
VL - 27
SP - 622
EP - 632
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 2
ER -