The GRIMs: a new interface between cell death regulation and interferon/retinoid induced growth suppression.
Cytokines and vitamins play a central role in controlling neoplastic cell growth. The interferon (IFN) family of cytokines regulates antiviral, anti-tumor, antimicrobial, differentiation, and immune responses in mammals. Significant advances have been made with respect to IFN-induced signal transduction pathways and antiviral responses. However, the IFN-induced anti-tumor actions are poorly defined. Although IFNs themselves inhibit tumor growth, combination of IFNs with retinoids (a class of Vitamin A related compounds) strongly potentiates the IFN-regulated anti-tumor action in a number of cell types. To define the molecular mechanisms involved in IFN/retinoid (RA)-induced apoptosis we have employed a genetic approach and identified several critical genes. In this review, I provide the current picture of IFN- RA- and IFN/RA-regulated growth suppressive pathways. In particular, I focus on a novel set of genes, the genes-associated with retinoid-interferon induced mortality (GRIM). GRIMs may be novel types of tumor suppressors, useful as biological response markers and potentially novel targets for drug development.
Kalvakolanu
Dhananjaya V
DV
Molecular and Cell Biology Graduate Program, Department of Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. dkalvako@umaryland.edu
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002455:Cell Division; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000502:physiology*; D012176:Retinoids / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D012176:Retinoids; D014157:Transcription Factors; D014212:Tretinoin; D007372:Interferons; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human