Regulation of serum response factor activity and smooth muscle cell apoptosis by chromodomain helicase DNA-binding protein 8

Jennifer M. Rodenberg, April M. Hoggatt, Meng Chen, Ketrija Touw, Rebekah Jones, B. Herring

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Serum response factor (SRF) is a widely expressed protein that plays a key role in the regulation of smooth muscle differentiation, proliferation, migration, and apoptosis. It is generally accepted that one mechanism by which SRF regulates these diverse functions is through pathwayspecific cofactor interactions. A novel SRF cofactor, chromodomain helicase DNA binding protein 8 (CHD8), was isolated from a yeast two-hybrid screen using SRF as bait. CHD8 is highly expressed in adult smooth muscle tissues. Coimmunoprecipitation assays from A10 smooth muscle cells demonstrated binding of endogenous SRF and CHD8. Data from GST-pulldown assays indicate that the NH 2-terminus of CHD8 can interact directly with the MADS domain of SRF. Adenoviral-mediated knockdown of CHD8 in smooth muscle cells resulted in attenuated expression of SRF-dependent, smooth muscle-specific genes. Knockdown of CHD8, SRF, or CTCF, a previously described binding partner of CHD8, in A10 VSMCs also resulted in a marked induction of apoptosis. Mechanistically, apoptosis induced by CHD8 knockdown was accompanied by attenuated expression of the anti-apoptotic proteins, Birc5, and CARD10, whereas SRF knockdown attenuated expression of CARD10 and Mcl-1, but not Birc5, and CTCF knockdown attenuated expression of Birc5. These data suggest that CHD8 plays a dual role in smooth muscle cells modulating SRF activity toward differentiation genes and promoting cell survival through interactions with both SRF and CTCF to regulate expression of Birc5 and CARD10.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume299
Issue number5
DOIs
StatePublished - Nov 2010

Fingerprint

Serum Response Factor
DNA-Binding Proteins
Smooth Muscle Myocytes
Apoptosis
Smooth Muscle
antineoplaston A10
Apoptosis Regulatory Proteins
Genes
Cell Survival

Keywords

  • Ternary complex factor
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Regulation of serum response factor activity and smooth muscle cell apoptosis by chromodomain helicase DNA-binding protein 8. / Rodenberg, Jennifer M.; Hoggatt, April M.; Chen, Meng; Touw, Ketrija; Jones, Rebekah; Herring, B.

In: American Journal of Physiology - Cell Physiology, Vol. 299, No. 5, 11.2010.

Research output: Contribution to journalArticle

Rodenberg, Jennifer M. ; Hoggatt, April M. ; Chen, Meng ; Touw, Ketrija ; Jones, Rebekah ; Herring, B. / Regulation of serum response factor activity and smooth muscle cell apoptosis by chromodomain helicase DNA-binding protein 8. In: American Journal of Physiology - Cell Physiology. 2010 ; Vol. 299, No. 5.
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