GRIM-19 associates with the serine protease HtrA2 for promoting cell death

X. Ma, S. Kalakonda, S. M. Srinivasula, S. P. Reddy, L. C. Platanias, D. V. Kalvakolanu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

We have isolated a novel interferon (IFN)-retinoid regulated cell death regulatory protein genes associated with retinoid-IFN-induced mortality (GRIM)-19 earlier. To understand its mechanism of action, we have employed a yeast-two-hybrid screen and identified serine protease HtrA2 as its binding partner. GRIM-19 physically interacts with HtrA2 and augments cell death in an IFN/all-trans retinoic acid (RA)-dependent manner. In the presence of GRIM-19, the HtrA2-driven destruction of the antiapoptotic protein X-linked inhibitor of apoptosis (XIAP) is augmented. These interactions were disrupted by an human herpes virus-8 (HHV-8)-coded oncoprotein, vIRF1, and conferred resistance to IFN/RA-induced cell death. These data show a critical role of HtrA2 in a cytokine-induced cell death response for the first time and its inhibition by a viral protein.

Original languageEnglish (US)
Pages (from-to)4842-4849
Number of pages8
JournalOncogene
Volume26
Issue number33
DOIs
StatePublished - Jul 19 2007

Funding

DVK thanks National Cancer Institute for grant support CA105005. We also thank Patrick Moore, Emad Alnemri and Margaret Offerman for providing the reagents used in this study.

Keywords

  • Cancer
  • Cell death
  • Cytokines
  • Growth suppression
  • Vitamins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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