STAT1 signaling is not regulated by a phosphorylation-acetylation switch
The treatment of cells with histone deacetylase inhibitors (HDACi) was reported to reveal the acetylation of STAT1 at lysine 410 and lysine 413 (O. H. Kra¨mer et al., Genes Dev. 20:473–485, 2006). STAT1 acetylation was proposed to regulate apoptosis by facilitating binding to NF-B and to control i...
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| Format: | Article |
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American Society for Microbiology
2011
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| Online Access: | https://eprints.nottingham.ac.uk/2936/ |
| _version_ | 1848790912802488320 |
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| author | Antunes, Filipa Marg, Andreas Vinkemeier, Uwe |
| author_facet | Antunes, Filipa Marg, Andreas Vinkemeier, Uwe |
| author_sort | Antunes, Filipa |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The treatment of cells with histone deacetylase inhibitors (HDACi) was reported to reveal the acetylation of
STAT1 at lysine 410 and lysine 413 (O. H. Kra¨mer et al., Genes Dev. 20:473–485, 2006). STAT1 acetylation was
proposed to regulate apoptosis by facilitating binding to NF-B and to control immune responses by suppressing
STAT1 tyrosine phosphorylation, suggesting that STAT1 acetylation is a central mechanism by which
histone deacetylase inhibitors ameliorate inflammatory diseases (O. H. Kra¨mer et al., Genes Dev. 23:223–235,
2009). Here, we show that the inhibition of deacetylases had no bearing on STAT1 acetylation and did not
diminish STAT1 tyrosine phosphorylation. The glutamine mutation of the alleged acetylation sites, claimed to
mimic acetylated STAT1, similarly did not diminish the tyrosine phosphorylation of STAT1 but precluded its
DNA binding and nuclear import. The defective transcription activity of this mutant therefore cannot be
attributed to STAT1 acetylation but rather to the inactivation of the STAT1 DNA binding domain and its
nuclear import signal. Experiments with respective cDNAs provided by the authors of the studies mentioned
above confirmed the results reported here, further questioning the validity of the previous data. We conclude
that the effects and potential clinical benefits associated with histone deacetylase inhibition cannot be explained by promoting the acetylation of STAT1 at lysines 410 and 413. |
| first_indexed | 2025-11-14T18:20:09Z |
| format | Article |
| id | nottingham-2936 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:20:09Z |
| publishDate | 2011 |
| publisher | American Society for Microbiology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-29362020-05-04T20:23:13Z https://eprints.nottingham.ac.uk/2936/ STAT1 signaling is not regulated by a phosphorylation-acetylation switch Antunes, Filipa Marg, Andreas Vinkemeier, Uwe The treatment of cells with histone deacetylase inhibitors (HDACi) was reported to reveal the acetylation of STAT1 at lysine 410 and lysine 413 (O. H. Kra¨mer et al., Genes Dev. 20:473–485, 2006). STAT1 acetylation was proposed to regulate apoptosis by facilitating binding to NF-B and to control immune responses by suppressing STAT1 tyrosine phosphorylation, suggesting that STAT1 acetylation is a central mechanism by which histone deacetylase inhibitors ameliorate inflammatory diseases (O. H. Kra¨mer et al., Genes Dev. 23:223–235, 2009). Here, we show that the inhibition of deacetylases had no bearing on STAT1 acetylation and did not diminish STAT1 tyrosine phosphorylation. The glutamine mutation of the alleged acetylation sites, claimed to mimic acetylated STAT1, similarly did not diminish the tyrosine phosphorylation of STAT1 but precluded its DNA binding and nuclear import. The defective transcription activity of this mutant therefore cannot be attributed to STAT1 acetylation but rather to the inactivation of the STAT1 DNA binding domain and its nuclear import signal. Experiments with respective cDNAs provided by the authors of the studies mentioned above confirmed the results reported here, further questioning the validity of the previous data. We conclude that the effects and potential clinical benefits associated with histone deacetylase inhibition cannot be explained by promoting the acetylation of STAT1 at lysines 410 and 413. American Society for Microbiology 2011-07 Article PeerReviewed Antunes, Filipa, Marg, Andreas and Vinkemeier, Uwe (2011) STAT1 signaling is not regulated by a phosphorylation-acetylation switch. Molecular and Cellular Biology, 31 (14). pp. 3029-3037. ISSN 0270-7306 http://mcb.asm.org/content/31/14/3029. doi:10.1128/MCB.05300-11 doi:10.1128/MCB.05300-11 |
| spellingShingle | Antunes, Filipa Marg, Andreas Vinkemeier, Uwe STAT1 signaling is not regulated by a phosphorylation-acetylation switch |
| title | STAT1 signaling is not regulated by a
phosphorylation-acetylation switch |
| title_full | STAT1 signaling is not regulated by a
phosphorylation-acetylation switch |
| title_fullStr | STAT1 signaling is not regulated by a
phosphorylation-acetylation switch |
| title_full_unstemmed | STAT1 signaling is not regulated by a
phosphorylation-acetylation switch |
| title_short | STAT1 signaling is not regulated by a
phosphorylation-acetylation switch |
| title_sort | stat1 signaling is not regulated by a
phosphorylation-acetylation switch |
| url | https://eprints.nottingham.ac.uk/2936/ https://eprints.nottingham.ac.uk/2936/ https://eprints.nottingham.ac.uk/2936/ |