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 journalArticle

30 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

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ma, X., Kalakonda, S., Srinivasula, S. M., Reddy, S. P., Platanias, L. C., & Kalvakolanu, D. V. (2007). GRIM-19 associates with the serine protease HtrA2 for promoting cell death. Oncogene, 26(33), 4842-4849. https://doi.org/10.1038/sj.onc.1210287