Tumor-suppressor genes: news about the interferon connection.
The interferons are a family of secreted, multifunctional proteins which are components of the defenses of vertebrates against viral, bacterial, and parasitic infections and certain tumors. They exert their various activities by inducing the synthesis of a large variety of proteins. There are direct and indirect indications that several of these proteins may have tumor-suppressor activities. The interferon-inducible proteins implicated include: (i) a double-stranded RNA-activatable protein kinase that can phosphorylate and thereby inactivate the eukaryotic peptide chain initiation factor eIF-2; (ii) the interferon regulatory factors IRF-1 and IRF-2, which can modulate the expression of the interferons and of some interferon-inducible proteins; and (iii) RNase L, a latent endoribonuclease which can be activated by (2'-5')oligoadenylates, the products of a family of enzymes which are also interferon-inducible. It is note-worthy that some of the proteins encoded by tumor virus oncogenes (e.g., E1A from adenovirus, EBNA-2 from Epstein-Barr virus, and terminal protein from hepatitis B virus) impair the induction of at least some proteins by interferons.
Lengyel
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Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004722:Endoribonucleases / Q000235:genetics / Q000502:physiology; D019309:Epstein-Barr Virus Nuclear Antigens; D016147:Genes, Tumor Suppressor; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D019892:eIF-2 Kinase
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease