title: MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.
abstract: Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea.|Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea.|KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Korea.
authors.forename: An Hue Vy
authors.identifier: 0000-0003-1960-6523
authors.initials: AHV
authors.lastname: Tran
authors.affiliation: Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea.
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Han
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences and Biotechnology and BioInstitute, Korea University, Seoul, Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Lazio, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grasso
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea.|KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Korea.
authors.forename: In San
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea.
authors.forename: Ye Sun
authors.initials: YS
authors.lastname: Han
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D051379:Mice; D009336:Necrosis / Q000139:chemically induced*; D011485:Protein Binding; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D053199:TNF Receptor-Associated Death Domain Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D047888:Receptors, Tumor Necrosis Factor, Type I; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D053181:Caspase 8; D002166:Camptothecin
keywords: NECROPTOSIS; TUMOR NECROSIS FACTOR ALPHA (TNF-α); TUMOR NECROSIS FACTOR RECEPTOR TYPE 1-ASSOCIATED DEATH DOMAIN (TRADD); mutY DNA GLYCOSYLASE (MYH)