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

The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins.

Author information

1
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

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.

PMID:
21166594
PMCID:
PMC3021352
DOI:
10.1089/jir.2010.0100
[Indexed for MEDLINE]
Free PMC Article

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