Acetylation of Stat1 modulates NF-κB activity
Open Access
- 15 February 2006
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 20 (4) , 473-485
- https://doi.org/10.1101/gad.364306
Abstract
Acetylation of signaling molecules can lead to apoptosis or differentiation of carcinoma cells. The molecular mechanisms underlying these processes and the biological role of enzymes mediating the transfer or removal of an acetyl-group are currently under intense investigation. Our study shows that Stat1 is an acetylated protein. Stat1 acetylation depends on the balance between Stat1-associated histone deacetylases (HDACs) and histone acetyltransferases (HATs) such as CBP. Remarkably both inhibitors of HDACs and the cytokine interferon α alter this equilibrium and induce Stat1 acetylation. The analysis of Stat1 mutants reveals Lys 410 and Lys 413 as acetylation sites. Experiments with Stat1 mutants mimicking either constitutively acetylated or nonacetylated states show that only acetylated Stat1 is able to interact with NF-κB p65. As a consequence, p65 DNA binding, nuclear localization, and expression of anti-apoptotic NF-κB target genes decrease. These findings show how the acetylation of Stat1 regulates NF-κB activity and thus ultimately apoptosis.Keywords
This publication has 59 references indexed in Scilit:
- Progressive dysregulation of transcription factors NF-κB and STAT1 in prostate cancer cells causes proangiogenic production of CXC chemokinesAmerican Journal of Physiology-Cell Physiology, 2004
- Histone Deacetylase Is a Target of Valproic Acid-Mediated Cellular DifferentiationCancer Research, 2004
- Interferon-γ Interferes with Transforming Growth Factor-β Signaling through Direct Interaction of YB-1 with Smad3Journal of Biological Chemistry, 2003
- Ineffectiveness of Histone Deacetylase Inhibitors to Induce Apoptosis Involves the Transcriptional Activation of NF-κB through the Akt PathwayJournal of Biological Chemistry, 2003
- Post-activation Turn-off of NF-κB-dependent Transcription Is Regulated by Acetylation of p65Journal of Biological Chemistry, 2003
- Isolation and Characterization of a Human STAT1Gene Regulatory ElementPublished by Elsevier ,2002
- Dissociation Time from DNA Determines Transcriptional Function in a STAT1 Linker MutantPublished by Elsevier ,2002
- How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 geneThe EMBO Journal, 2000
- The language of covalent histone modificationsNature, 2000
- Site-directed mutagenesis by overlap extension using the polymerase chain reactionGene, 1989