Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes

Wendy M. McKimpson, Yun Chen, James A. Irving, Min Zheng, Jeremy Weinberger, Wilson Lek Wen Tan, Zenia Tiang, Alistair M. Jagger, Streamson C. Chua, Jeffrey E. Pessin, Roger S.Y. Foo, David A. Lomas, Richard N. Kitsis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

While cytoplasmic ARC maintains survival of insulin-producing pancreatic β cells, McKimpson et al. show that a pool of ARC relocates to the nucleus during diabetes where it paradoxically triggers cell death. The mechanism involves downregulation of AAT expression and secretion unleashing elastase-dependent loss of β cell adhesion and cell death.

Original languageEnglish (US)
Pages (from-to)747-760.e6
JournalDevelopmental cell
Volume56
Issue number6
DOIs
StatePublished - Mar 22 2021

Keywords

  • ARC
  • alpha-1 antitrypsin
  • cell death
  • diabetes
  • serpins

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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