STAT1 signaling is not regulated by a phosphorylation-acetylation switch

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

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Biomedical Sciences
Identification Number:
Depositing User: de Sousa, Mrs Shona
Date Deposited: 10 Apr 2014 10:28
Last Modified: 04 May 2020 20:23

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