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ERK-mediated phosphorylation of BIS regulates nuclear translocation of HSF1 under oxidative stress.
Kim, Hye Yun; Kim, Yong-Sam; Yun, Hye Hyeon; Im, Chang-Nim; Ko, Jeong-Heon; Lee, Jeong-Hwa.
Afiliação
  • Kim HY; Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Kim YS; Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Yun HH; Aging Intervention Research Center, Aging Research Institute, KRIBB, Daejeon, Republic of Korea.
  • Im CN; Korea University of Science and Technology. Daejeon, Republic of Korea.
  • Ko JH; Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Lee JH; Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Exp Mol Med ; 48(9): e260, 2016 Sep 23.
Article em En | MEDLINE | ID: mdl-27659916
B-cell lymphoma (BCL)-2-interacting cell death suppressor (BIS) has diverse cellular functions depending on its binding partners. However, little is known about the effects of biochemical modification of BIS on its various activities under oxidative stress conditions. In this study, we showed that H2O2 reduced BIS mobility on SDS-polyacrylamide gels in a time-dependent manner via the activation of extracellular signaling-regulated kinase (ERK). The combined results of mass spectroscopy and computational prediction identified Thr285 and Ser289 in BIS as candidate residues for phosphorylation by ERK under oxidative stress conditions. Deletion of these sites resulted in a partial reduction in the H2O2-induced mobility shift relative to that of the wild-type BIS protein; overexpression of the deletion mutant sensitized A172 cells to H2O2-induced cell death without increasing the level of intracellular reactive oxygen species. Expression of the BIS deletion mutant decreased the level of heat shock protein (HSP) 70 mRNA following H2O2 treatment, which was accompanied by impaired nuclear translocation of heat shock transcription factor (HSF) 1. Co-immunoprecipitation assays revealed that the binding of wild-type BIS to HSF1 was decreased by oxidative stress, while the binding of the BIS deletion mutant to HSF1 was not affected. These results indicate that ERK-dependent phosphorylation of BIS has a role in the regulation of nuclear translocation of HSF1 likely through modulation of its interaction affinity with HSF1, which affects HSP70 expression and sensitivity to oxidative stress.

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article