title: Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation.
abstract: Thioredoxin 1 (Trx1) is а 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 mice with cardiac-specific over-expression of Trx1, an animal model that has been proven to withstand 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-translational modification, via the regulation of SMYD1 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.
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Changgong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Mohit Raja
authors.initials: MR
authors.lastname: Jain
authors.affiliation: Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers University-New Jersey Medical School, Newark, NJ 07103, United States.
authors.forename: Narayani
authors.initials: N
authors.lastname: Nagarajan
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Huacheng
authors.initials: H
authors.lastname: Dai
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Chuanlong
authors.initials: C
authors.lastname: Cui
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Baykal
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States.
authors.forename: Stacey
authors.initials: S
authors.lastname: Pan
authors.affiliation: Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers University-New Jersey Medical School, Newark, NJ 07103, United States.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ago
authors.affiliation: Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers University-New Jersey Medical School, Newark, NJ 07103, United States.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
authors.affiliation: Center for Advanced Proteomics Research, Department of Biochemistry and Molecular Biology, Rutgers University-New Jersey Medical School Cancer Center, Newark, NJ 07103, United States. Electronic address: liho2@rutgers.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000502:physiology*; D010084:Oxidation-Reduction; D013879:Thioredoxins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C096485:Smyd1 protein, mouse; D014157:Transcription Factors; D013879:Thioredoxins; D008239:Lysine
keywords: Mass spectrometry; Methylation; Thioredoxin; iTRAQ