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PMID: 21166594 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

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

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research ·Vol. 31 ·No. 1 ·2011-01-00 ·Pages 33-40

Cheon H, Yang J, Stark GR

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.

MeSH Terms
Animals Antineoplastic Agents/pharmacology,therapeutic use Antiviral Agents/pharmacology,therapeutic use Cytokines/metabolism Gene Expression Regulation/drug effects Humans Immunity, Innate/drug effects Interferons/pharmacology,therapeutic use Multiple Sclerosis/drug therapy,immunology Neoplasms/drug therapy,metabolism Phosphorylation/drug effects Protein Processing, Post-Translational/drug effects STAT1 Transcription Factor/genetics,metabolism STAT3 Transcription Factor/genetics,metabolism Virus Diseases/drug therapy,immunology,metabolism
Chemicals
Antineoplastic Agents Antiviral Agents Cytokines STAT1 Transcription Factor STAT3 Transcription Factor Interferons
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cheon Hyeonjoo
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Yang Jinbo
Stark George R
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Article Info
Journal
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
Abbr.
J Interferon Cytokine Res
ISSN
1557-7465
DOI
10.1089/jir.2010.0100
Published
2011-01-00
Epub
2010-00-19
Pages
33-40
Language
English
Region
United States
NLM ID
9507088
PMCID
PMC3021352
Subset
IM
Grants
NCI NIH HHS · P01 CA62220 · United States
External Links
PubMed source DOI: 10.1089/jir.2010.0100 PMC Full Text View journal details
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