Cytokine-induced tumor suppressors: A GRIM story

Cytokines belonging to the IFN family are potent growth suppressors. In a number of clinical and preclinical studies, vitamin A and its derivatives like retinoic acid (RA) have been shown to exert synergistic growth-suppressive effects on several tumor cells. We have employed a genome-wide expression-knockout approach to identify the genes critical for IFN/RA-induced growth suppression. A number of novel genes associated with Retinoid-Interferon-induced Mortality (GRIM) were isolated. In this review, we will describe the molecular mechanisms of actions of one, GRIM-19, which participates in multiple pathways for exerting growth control and/or cell death. This protein is emerging as a new tumor suppressor. In addition, GRIM-19 appears to participate in innate immune responses as its activity is modulated by several viruses and bacteria. Thus, GRIMs seem to couple with multiple biological responses by acting at critical nodes. (C) 2010 Elsevier Ltd. All rights reserved.