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

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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalCellular Signalling
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Keywords

  • Airway
  • Glutathionylation
  • Major vault protein
  • Myosin-9
  • Redox signaling
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cell Biology

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