Repression of smooth muscle differentiation by a novel high mobility group box-containing protein, HMG2L1

Jiliang Zhou, Guoqing Hu, Xiaobo Wang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The molecular mechanisms regulating smooth muscle-specific gene expression during smooth muscle development are poorly understood. Myocardin is an extraordinarily powerful cofactor of serum response factor (SRF) that stimulates expression of smooth muscle-specific genes. In an effort to search for proteins that regulate myocardin function, we identified a novel HMG box-containing protein HMG2L1 (high mobility group 2 like 1). We found that HMG2L1 expression is correlated with the smooth muscle cell (SMC) synthetic phenotype. Overexpression of HMG2L1 in SMCs down-regulated smooth muscle marker expression. Conversely, depletion of endogenousHMG2L1inSMCsincreases smooth muscle-specific gene expression. Furthermore, we found HMG2L1 specifically abrogates myocardin-induced activation of smooth muscle-specific genes. By GST pulldown assays, the interaction domains between HMG2L1 and myocardin were mapped to the N termini of each of the proteins. Finally, we demonstrated that HMG2L1 abrogates myocardin function through disrupting its binding to SRF and abolishing SRF-myocardin complex binding to the promoters of smooth muscle-specific genes. This study provides the first evidence of this novel HMG2L1 molecule playing an important role in attenuating smooth muscle differentiation.

Original languageEnglish (US)
Pages (from-to)23177-23185
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number30
DOIs
StatePublished - Jul 23 2010

Fingerprint

HMGB Proteins
High Mobility Group Proteins
Smooth Muscle
Muscle
Serum Response Factor
Genes
Gene expression
Gene Expression
Muscle Development
Smooth Muscle Myocytes
myocardin
Proteins
Assays
Chemical activation
Phenotype
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Repression of smooth muscle differentiation by a novel high mobility group box-containing protein, HMG2L1. / Zhou, Jiliang; Hu, Guoqing; Wang, Xiaobo.

In: Journal of Biological Chemistry, Vol. 285, No. 30, 23.07.2010, p. 23177-23185.

Research output: Contribution to journalArticle

@article{cb378e6712b7483e906416950dacdfb7,
title = "Repression of smooth muscle differentiation by a novel high mobility group box-containing protein, HMG2L1",
abstract = "The molecular mechanisms regulating smooth muscle-specific gene expression during smooth muscle development are poorly understood. Myocardin is an extraordinarily powerful cofactor of serum response factor (SRF) that stimulates expression of smooth muscle-specific genes. In an effort to search for proteins that regulate myocardin function, we identified a novel HMG box-containing protein HMG2L1 (high mobility group 2 like 1). We found that HMG2L1 expression is correlated with the smooth muscle cell (SMC) synthetic phenotype. Overexpression of HMG2L1 in SMCs down-regulated smooth muscle marker expression. Conversely, depletion of endogenousHMG2L1inSMCsincreases smooth muscle-specific gene expression. Furthermore, we found HMG2L1 specifically abrogates myocardin-induced activation of smooth muscle-specific genes. By GST pulldown assays, the interaction domains between HMG2L1 and myocardin were mapped to the N termini of each of the proteins. Finally, we demonstrated that HMG2L1 abrogates myocardin function through disrupting its binding to SRF and abolishing SRF-myocardin complex binding to the promoters of smooth muscle-specific genes. This study provides the first evidence of this novel HMG2L1 molecule playing an important role in attenuating smooth muscle differentiation.",
author = "Jiliang Zhou and Guoqing Hu and Xiaobo Wang",
year = "2010",
month = "7",
day = "23",
doi = "10.1074/jbc.M110.109868",
language = "English (US)",
volume = "285",
pages = "23177--23185",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

TY - JOUR

T1 - Repression of smooth muscle differentiation by a novel high mobility group box-containing protein, HMG2L1

AU - Zhou, Jiliang

AU - Hu, Guoqing

AU - Wang, Xiaobo

PY - 2010/7/23

Y1 - 2010/7/23

N2 - The molecular mechanisms regulating smooth muscle-specific gene expression during smooth muscle development are poorly understood. Myocardin is an extraordinarily powerful cofactor of serum response factor (SRF) that stimulates expression of smooth muscle-specific genes. In an effort to search for proteins that regulate myocardin function, we identified a novel HMG box-containing protein HMG2L1 (high mobility group 2 like 1). We found that HMG2L1 expression is correlated with the smooth muscle cell (SMC) synthetic phenotype. Overexpression of HMG2L1 in SMCs down-regulated smooth muscle marker expression. Conversely, depletion of endogenousHMG2L1inSMCsincreases smooth muscle-specific gene expression. Furthermore, we found HMG2L1 specifically abrogates myocardin-induced activation of smooth muscle-specific genes. By GST pulldown assays, the interaction domains between HMG2L1 and myocardin were mapped to the N termini of each of the proteins. Finally, we demonstrated that HMG2L1 abrogates myocardin function through disrupting its binding to SRF and abolishing SRF-myocardin complex binding to the promoters of smooth muscle-specific genes. This study provides the first evidence of this novel HMG2L1 molecule playing an important role in attenuating smooth muscle differentiation.

AB - The molecular mechanisms regulating smooth muscle-specific gene expression during smooth muscle development are poorly understood. Myocardin is an extraordinarily powerful cofactor of serum response factor (SRF) that stimulates expression of smooth muscle-specific genes. In an effort to search for proteins that regulate myocardin function, we identified a novel HMG box-containing protein HMG2L1 (high mobility group 2 like 1). We found that HMG2L1 expression is correlated with the smooth muscle cell (SMC) synthetic phenotype. Overexpression of HMG2L1 in SMCs down-regulated smooth muscle marker expression. Conversely, depletion of endogenousHMG2L1inSMCsincreases smooth muscle-specific gene expression. Furthermore, we found HMG2L1 specifically abrogates myocardin-induced activation of smooth muscle-specific genes. By GST pulldown assays, the interaction domains between HMG2L1 and myocardin were mapped to the N termini of each of the proteins. Finally, we demonstrated that HMG2L1 abrogates myocardin function through disrupting its binding to SRF and abolishing SRF-myocardin complex binding to the promoters of smooth muscle-specific genes. This study provides the first evidence of this novel HMG2L1 molecule playing an important role in attenuating smooth muscle differentiation.

UR - http://www.scopus.com/inward/record.url?scp=77954910387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954910387&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.109868

DO - 10.1074/jbc.M110.109868

M3 - Article

C2 - 20511232

AN - SCOPUS:77954910387

VL - 285

SP - 23177

EP - 23185

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -