Major vault protein regulates cell growth/survival signaling through oxidative modifications

Dividutta Das, Yi Hsuan Wang, Cheng Ying Hsieh, Yuichiro J. Suzuki

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

摘要

Major vault protein forms a hollow, barrel-like structure in the cell called the vault, whose functions and regulation are not well understood. The present study reports that major vault protein regulates growth/survival signaling in human airway smooth muscle cells through oxidative modifications. The promotion of protein S-glutathionylation by asthma mediators such as interleukin-22 and platelet-derived growth factor or by knocking down glutaredoxin-1 or thioredoxin activated cell growth signaling. Mass spectrometry identified that major vault protein is glutathionylated. Major vault protein knockdown enhanced cell death and inhibited STAT3 and Akt signaling. We identified a protein partner of major vault protein that is regulated by glutaredoxin-1, namely myosin-9, which was found to serve as a cell death factor. Knocking down myosin-9 or promoting protein S-glutathionylation by knocking down glutaredoxin-1 inhibited the death of airway smooth muscle cells by heating to simulate bronchial thermoplasty, a clinically successful procedure for the treatment of severe asthma. These results establish a novel signaling pathway in which ligand/receptor-mediated oxidation promotes the S-glutathionylation of major vault protein, which in turn binds to myosin-9 to suppress the heating-induced death of airway smooth muscle cells.

原文英語
頁(從 - 到)12-18
頁數7
期刊Cellular Signalling
28
發行號1
DOIs
出版狀態已發佈 - 1月 1 2016
對外發佈

ASJC Scopus subject areas

  • 細胞生物學

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