Myocardin in biology and disease

Abstract

Myocardin (MYOCD) is a potent transcriptional coactivator that functions primarily in cardiac muscle and smooth muscle through direct contacts with serum response factor (SRF) over cis elements known as CArG boxes found near a number of genes encoding for contractile, ion channel, cytoskeletal, and calcium handling proteins. Since its discovery more than 10 years ago, new insights have been obtained regarding the diverse isoforms of MYOCD expressed in cells as well as the regulation of MYOCD expression and activity through transcriptional, post-transcriptional, and post-translational processes. Curiously, there are a number of functions associated with MYOCD that appear to be independent of contractile gene expression and the CArG-SRF nucleoprotein complex. Further, perturbations in MYOCD gene expression are associated with an increasing number of diseases including heart failure, cancer, acute vessel disease, and diabetes. This review summarizes the various biological and pathological processes associated with MYOCD and offers perspectives to several challenges and future directions for further study of this formidable transcriptional coactivator.

Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

“…Postnatal cardio-restricted MYOCD knockdown induces dilated cardiomyopathy and fatal HF in mice [69], while forced expression of MYOCD in ventricular myocardium impairs LV systolic function and cardiac ECG activity in pigs [70]. In light of these results, it comes as no surprise that a strong association between the altered expression of MYOCD and cardiac pathological conditions has been established in different animal models as well as patients with end-stage HF (reviewed in [23,67,68]). …”

“…One of such cofactors is myocardin (MYOCD) that regulates the expression of multiple smooth muscle (SM) and cardiac contractile genes, including CNN1 (calponin 1, basic, smooth muscle), MYH11 (myosin, heavy chain 11, smooth muscle), ACTA2 (actin, alpha 2, smooth muscle, aorta), ACTG2 (actin, gamma 2, smooth muscle), TAGLN (transgelin), and MYH6 (myosin, heavy chain 6, cardiac muscle, alpha) (reviewed in [23,[65][66][67][68]). …”

“…b Combinatorial TF interactions. Schematic illustrates TBX5::GATA4 [130], TBX5::GATA-6 [131], TBX5::MYOCD [132], GATA-4::GATA-6 [54], SRF::MYOCD [68], SRF::PITX2 [133], PIXT2::GATA-4 [134], and PITX2::NRF2 [82] proteinprotein interactions that lead to cooperative regulation of target gene expression in vitro. c TBX5 [29], GATA-4 [135], SRF [136], MYOCD [137], NRF2 [138], and PITX2 [97] are coexpressed in the adult human left ventricle (LV), suggesting that the interplay of these TFs in vitro (shown in b) also takes place in vivo (data for GATA-6 equivalent to those for GATA-4 are currently lacking).…”

Angiogenic Factor With G Patch and FHA Domains 1 Is a Novel Regulator of Vascular Injury

“…Many previously characterized myocardin-associated factors either stabilize or disrupt the SRF-myocardin complex. 8 It is likely that Aggf1 may function as a scaffold to bring SRF and myocardin together. Alternatively, the ability of myocardin to associate with SRF is known to be modulated by post-translational modifications.…”

“…Alternatively, the ability of myocardin to associate with SRF is known to be modulated by post-translational modifications. 8,17 It has recently been shown that Aggf1 is able to modulate the activities of several kinases including extracellular signal-regulated kinase 18 Figure 3. Angiogenic factor with G patch and FHA domains 1 (Aggf1) is essential for serum response factor (SRF)-dependent transactivation of smooth muscle cell-specific genes.…”