Interferon induced growth suppression: a GRIM path

Interferons and their combination with other biological response modifiers potently suppress cell growth. Using a genome‐wide knock down approach, we identified novel genes that play critical roles in Interferon‐induced growth suppression. One such gene GRIM‐19 appears to integrate into multiple pathways to suppress tumor growth. GRIM‐19 interferes with transactivation function of STAT3 to suppress tumor growth and survival. It inhibits cell cycle progression by interacting with the CDK‐inhibitor p16Ink4a, a known tumor suppressor. GRIM‐19 reverses src‐oncogene induced cytoskeletal remodeling. In addition, the viral oncogenes vIRF1 of KSHV and E6 of High‐Risk Human Papilloma viruses interact with GRIM‐19 and inactivate its growth suppressive function. Consistent with its anti‐tumor properties, the expression of GRIM‐19 is either lost or the GRIM‐19 gene is mutated in many human cancers. Together, these data establish GRIM‐19 as a novel tumor suppressor. The biological effects GRIM‐19 and consequences of mutations on tumorigenesis will be discussed.