Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death.
Kaposi's sarcoma-associated herpesvirus (KSHV) plays a significant role in the development of Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman's disease. The KSHV open reading frame K9 encodes the viral interferon (IFN) factor 1 (vIRF1), which downregulates IFN- and IRF-mediated transcriptional activation, and leads to cellular transformation in rodent fibroblasts and induction of tumors in nude mice. Using the yeast two-hybrid assay, we identified genes associated with retinoid-IFN-induced mortality-19 (GRIM19), which interacts directly with vIRF1, both in vivo and in vitro. The N-terminal region of vIRF1 is required for binding GRIM19. Colocalization of vIRF1 and GRIM19 was observed in 293T cells. The vIRF1 protein deregulates GRIM19-induced apoptosis in the presence of IFN/all-trans-retinoic acid (RA) and inhibits IFN/RA-induced cell death. Another DNA tumor viral protein, human papillomavirus type 16 E6, also binds GRIM19, suggesting that this is a general target of viral proteins. Our results collectively indicate that vIRF1 modulates IFN/RA-cell death signals via interactions with GRIM19.
Seo
Taegun
T
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Lee
Daeyoup
D
Shim
Young Sam
YS
Angell
Jon E
JE
Chidambaram
Natesa V
NV
Kalvakolanu
Dhananjaya V
DV
Choe
Joonho
J
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D050835:Interferon Regulatory Factors; D016899:Interferon-beta / Q000494:pharmacology; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D013347:Subcellular Fractions; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D050835:Interferon Regulatory Factors; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C413486:viral interferon regulatory factors; D014212:Tretinoin; D016899:Interferon-beta; D009247:NADH, NADPH Oxidoreductases; C486684:Grim19 protein, mouse; C439057:NDUFA13 protein, human