title: The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins.
abstract: The signal transducers and activators of transcription (STAT)1 and STAT3 genes are specifically activated by phosphorylated STATs 1 and 3, respectively, resulting in large and prolonged increases in the levels of unphosphorylated STATs (U-STATs) in response to interferons (for STAT1) or ligands that activate gp130, such as IL-6 (for STAT3). U-STATs 1 and 3 are transcription factors that drive gene expression by mechanisms distinct from those used by phosphorylated STATs. U-STAT3 drives expression of many proteins not induced by phospho-STAT3, including several that are important in tumorigenesis. U-STAT1 prolongs and increases expression of a subset of proteins induced initially in response to phospho-STAT1, leading to antiviral and immune responses that are long-lived. U-STAT1 levels are also high in some cancers, and the protein products of genes induced by U-STAT1 enhance resistance to DNA damage. Therefore, interferons not only drive short-term expression of proteins that inhibit growth and promote apoptosis and immune surveillance, but also promote long-term expression of proteins that facilitate tumor survival.
authors.affiliation: Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Hyeonjoo
authors.initials: H
authors.lastname: Cheon
authors.forename: Jinbo
authors.initials: J
authors.lastname: Yang
authors.forename: George R
authors.initials: GR
authors.lastname: Stark
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014777:Virus Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D016207:Cytokines; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D007372:Interferons