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 language | English (US) |
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Pages (from-to) | 4842-4849 |
Number of pages | 8 |
Journal | Oncogene |
Volume | 26 |
Issue number | 33 |
DOIs | |
State | Published - 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