Cell Division Cycle 7 Mediates Transforming Growth Factor-β-induced Smooth Muscle Maturation through Activation of Myocardin Gene Transcription

Shi, Ning; Chen, Shiyou

doi:10.1074/jbc.m113.498238

Cited by 12 publications

(12 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…D). Transcription factor NKX2.5 was demonstrated to be an activator for myocardin expression both in cardiomyocytes and SMCs and a NKX2.5 binding element (NKE) was conserved in the myocardin promoter. Myocardin promoter luciferase plasmid with mutated NKX2.5 binding element was cotransfected with pcDNA‐YAP construct.…”

Section: Resultssupporting

confidence: 90%

“…Similarly, our results showed YAP negatively regulated function of myocardin and YAP attenuated function of myocardin by inhibiting transcription of myocardin in a dose and NKX2.5 dependent manner. As indicated herein, Nkx2.5 was an activator of myocardin transcription and important in the maturation of VSMCs, which is consistent with previous findings . Importantly, we found that protein‐protein interaction between YAP and NKX2.5 mediated YAP's inhibition on myocardin transcription and myocardin‐driven VSMC differentiation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage

et al. 2016

View full text Add to dashboard Cite

Vascular smooth muscle cells (VSMCs) derived from cardiovascular progenitor cell (CVPC) lineage populate the tunica media of the aortic root. Understanding differentiation of VSMCs from CVPC will further our understanding of the molecular mechanisms contributing to aortic root aneurysms, and thus, facilitate the development of novel therapeutic agents to prevent this devastating complication. It is established that the yes-associated protein (YAP) and Hippo pathway is important for VSMC proliferation and phenotype switch. To determine the role of YAP in differentiation of VSMCs from CVPCs, we utilized the in vitro monolayer lineage specific differentiation method by differentiating human embryonic stem cells into CVPCs, and then, into VSMCs. We found that expression of YAP decreased during differentiation of VSMC from CVPCs. Overexpression of YAP attenuated expression of VSMC contractile markers and impaired VSMC function. Knockdown of YAP increased expression of contractile proteins during CVPC-VSMCs differentiation. Importantly, expression of YAP decreased transcription of myocardin during this process. Overexpression of YAP in PAC1 SMC cell line inhibited luciferase activity of myocardin proximal promoter in a dose dependent and NKX2.5 dependent manner. YAP protein interacted with NKX2.5 protein and inhibited binding of NKX2.5 to the 5’-proximal promoter region of myocardin in CVPC-derived VSMCs. In conclusion, YAP negatively regulates differentiation of VSMCs from CVPCs by decreasing transcription of myocardin in a NKX2.5-dependent manner.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage

et al. 2016

View full text Add to dashboard Cite

show abstract

“…10T1/2 cells were cultured in DMEM and treated with or without TGF-␤ or other factors as needed. Total proteins were extracted as described previously (32). Nuclear and cytoplasmic proteins were extracted using nuclear extraction kit (EMD Millipore) according to the manufacturer's instructions.…”

Section: Western Blottingmentioning

confidence: 99%

Mesenchyme homeobox 1 mediates transforming growth factor-β (TGF-β)–induced smooth muscle cell differentiation from mouse mesenchymal progenitors

Dong

Guo

Chen

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Differentiation of smooth muscle cells (SMCs) is critical for proper vasculogenesis and angiogenesis. However, the molecular mechanisms controlling SMC differentiation are not completely understood. During embryogenesis, the transcription factor mesenchyme homeobox 1 (Meox1) is expressed in the early developing somite, which is one of the origins of SMCs. In the present study, we identified Meox1 as a positive regulator of SMC differentiation. We found that transforming growth factor-β (TGF-β) induces Meox1 expression in the initial phase of SMC differentiation of pluripotent murine C3H10T1/2 cells. shRNA-mediated Meox1 knockdown suppressed TGF-β-induced expression of SMC early markers, whereas Meox1 overexpression increased expression of these markers. Mechanistically, Meox1 promoted SMAD family member 3 (Smad3) nuclear retention during the early stage of TGF-β stimulation because Meox1 inhibited protein phosphatase Mg/Mn-dependent 1A (PPM1A) and thereby prevented PPM1A-mediated Smad3 dephosphorylation. Meox1 appears to promote PPM1A degradation, leading to sustained Smad3 phosphorylation, thus allowing Smad3 to stimulate SMC gene transcription. , Meox1 knockdown in mouse embryos impaired SMC marker expression in the descending aorta of neonatal mice, indicating that Meox1 is essential for SMC differentiation during embryonic development. In summary, the transcriptional regulator Meox1 controls TGF-β-induced SMC differentiation from mesenchymal progenitor cells by preventing PPM1A-mediated Smad3 dephosphorylation, thereby supporting SMC gene expression.

show abstract

“…The first positive-acting element described was a proximal binding site for the cardiac muscle-restricted transcription factor, NKX2-5[61]. The effect of NKX2-5 on Myocd promoter activity was further shown to be modulated either positively or negatively through direct interactions between NKX2-5 and either CDC7[62] or SMAD3[63], respectively. An upstream NFATc3 binding site was demonstrated in the rat Myocd promoter using ChIP assays and forced expression of constitutively active NFATc3 could stimulate both Myocd promoter activity and mRNA expression[64].…”

Section: Regulatory Control Of Myocardin Expression and Activitymentioning

confidence: 99%

Myocardin in biology and disease

Miano

2015

J Biomed Res

101

View full text Add to dashboard Cite

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.

show abstract

Cell Division Cycle 7 Mediates Transforming Growth Factor-β-induced Smooth Muscle Maturation through Activation of Myocardin Gene Transcription

Cited by 12 publications

References 39 publications

Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage

Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage

Mesenchyme homeobox 1 mediates transforming growth factor-β (TGF-β)–induced smooth muscle cell differentiation from mouse mesenchymal progenitors

Myocardin in biology and disease

Contact Info

Product

Resources

About