Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation

Tong Liu, Changgong Wu, Mohit Raja Jain, Narayani Nagarajan, Lin Yan, Huacheng Dai, Chuanlong Cui, Ahmet Baykal, Stacey Pan, Tetsuro Ago, Junichi Sadoshima, Hong Li

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Thioredoxin 1 (Trx1) is ? antioxidant protein that regulates protein disulfide bond reduction, transnitrosylation, denitrosylation and other redox post-translational modifications. In order to better understand how Trx1 modulates downstream protective cellular signaling events following cardiac ischemia, we conducted an expression proteomics study of left ventricles (LVs) after thoracic aortic constriction stress treatment of transgenic micewith cardiac-specific over-expression of Trx1, an animal model that has been proven towithstand more stress than its non-transgenic littermates. Although previous redox post-translational modifications proteomics studies found that several cellular protein networks are regulated by Trx1-mediated disulfide reduction and transnitrosylation, we found that Trx1 regulates the expression of a limited number of proteins. Among the proteins found to be upregulated in this study was SET and MYND domain-containing protein 1 (SMYD1), a lysine methyltransferase highly expressed in cardiac and other muscle tissues and an important regulator of cardiac development. The observation of SMYD1 induction by Trx1 following thoracic aortic constriction stress is consistent with the retrograde fetal gene cardiac protection hypothesis. The results presented here suggest for the first time that, in addition to being a master redox regulator of protein disulfide bonds and nitrosation, Trx1 may also modulate lysine methylation, a non-redox post-translationalmodification, via the regulation ofSMYD1 expression. Such crosstalk between redox signaling and a non-redox PTM regulation may provide novel insights into the functions of Trx1 that are independent from its immediate function as a protein reductase.

Original languageEnglish
Pages (from-to)1816-1822
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1854
Issue number12
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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