4.6 Article

Oxidative Stress Drives Disulfide Bond Formation Between Basic Helix-Loop-Helix Transcription Factors

期刊

JOURNAL OF CELLULAR BIOCHEMISTRY
卷 109, 期 2, 页码 417-424

出版社

WILEY
DOI: 10.1002/jcb.22415

关键词

bHLH TRANSCRIPTION FACTORS; HYDROGEN PEROXIDE; OXIDATIVE STRESS; DISULFIDE BONDS

资金

  1. NIH-NIDCR [5K22DE016614]
  2. NIH-NICHD [R01HD029468]

向作者/读者索取更多资源

Basic helix-loop-helix (bHLH) transcription factors including Twist1 and E2a proteins regulate essential processes. These factors bind DNA as homo- or heterodimers and the choice of binding partners determines their functional output. To investigate potential regulators of bHLH dimerization, cells were exposed to the oxidative agent hydrogen peroxide (H2O2). Western blot analysis in the presence or absence of reducing agents, revealed that H2O2. induces the rapid formation of an intermolecular disulfide bond between Twist 1 homodimers and Twist/E2a proteins heterodimers. This disulfide bond is first observed between Twist I homodimers at 25 mM H2O2 and Twist 1 heterodimers at 75 mM H2O2. This response is dependent upon cell density as H2O2 did not induce disulfide bridge Formation between bHLH proteins in cells seeded at high density. In the presence of E proteins, the formation of Twist 1/E2a proteins heterodimers is favored over Twist I homodimers, identifying in oxidative stimulus is all important Factor in modulating binding partner specificity. We further demonstrated that a cysteine residue located at the C-terminus of Twist1 and E2a proteins is involved in this response. Disulfide bond formation between Twist1 homodimers significantly reduced its ability to interact With two of its binding partners, Runx2 HDAC4, indicating that disulfide dimerization in response to H2O2 has functional significance. These data support the conclusion that disulfide bond formation in response to all oxidative stimulus contributes to Twist1 homo- and heterodimerization and raises the possibility that the redox status of a cell may represent in important step in transcriptional regulation. J. Cell. Biochem. 109: 417-424, 2010. (C) 2009 Wiley-Liss, Inc.

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