title: GRIM-19 in Health and Disease.
abstract: GRIM-19, a gene associated with retinoid interferon-induced mortality, was originally identified as a critical regulatory protein for interferon-beta and retinoic acid-induced cell death. It was also demonstrated that GRIM-19 is involved in mitochondrial metabolism, as an integrant component of complex I of the mitochondrial respiratory chain. GRIM-19 appears, therefore, as a dual function protein involved in cell death and mitochondrial metabolism. GRIM-19 knock out leads to Complex I assembly disruption and embryonic lethality in mice, showing that it is a crucial component of the mitochondrial respiratory chain essential for early embryonic development. Recently, mutations in GRIM-19 were described in Hürthle cell (mitochondrion-rich) tumors of the thyroid and down-regulation or loss of its expression were found in renal cell carcinomas, suggesting a role for GRIM-19 in tumorigenesis. As GRIM-19 binds and inhibits the signal transducer and activator of transcription-3 (STAT3), which has been shown to be activated in several human tumors it is tempting to advance that GRIM-19 may function as a tumor suppressor gene in tumors in which STAT3 plays a major role.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, Porto, Portugal.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: André
authors.initials: A
authors.lastname: Silva
authors.forename: Inês
authors.initials: I
authors.lastname: Bento
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human