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ERK-mediated phosphorylation of BIS regulates nuclear translocation of HSF1 under oxidative stress
Experimental & Molecular Medicine ; : e260-2016.
Article in English | WPRIM | ID: wpr-117336
ABSTRACT
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Phosphotransferases / Shock / Mass Spectrometry / Transcription Factors / RNA, Messenger / Lymphoma, B-Cell / Cell Death / Reactive Oxygen Species / Oxidative Stress Type of study: Prognostic study Language: English Journal: Experimental & Molecular Medicine Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Phosphotransferases / Shock / Mass Spectrometry / Transcription Factors / RNA, Messenger / Lymphoma, B-Cell / Cell Death / Reactive Oxygen Species / Oxidative Stress Type of study: Prognostic study Language: English Journal: Experimental & Molecular Medicine Year: 2016 Type: Article