The Functions of Signal Transducers and Activators of Transcriptions 1 and 3 as Cytokine-Inducible Proteins

J Interferon Cytokine Res. 2011 Jan;31(1):33-40. doi: 10.1089/jir.2010.0100. Epub 2010 Dec 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cytokines / metabolism*
  • Gene Expression Regulation* / drug effects
  • Humans
  • Immunity, Innate / drug effects
  • Interferons / pharmacology
  • Interferons / therapeutic use
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Virus Diseases / drug therapy
  • Virus Diseases / immunology
  • Virus Diseases / metabolism

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Cytokines
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Interferons