Acetylation modulates the STAT signaling code

Abstract A fascinating question of modern biology is how a limited number of signaling pathways generate biological diversity and crosstalk phenomena in vivo . Well-defined posttranslational modification patterns dictate the functions and interactions of proteins. The signal transducers and activato...

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Bibliographic Details
Published in:Cytokine & growth factor reviews 2012-12, Vol.23 (6), p.293-305
Main Authors: Wieczorek, Martin, Ginter, Torsten, Brand, Peter, Heinzel, Thorsten, Krämer, Oliver H
Format: Article
Language:English
Subjects:
Acetylation
Advanced Basic Science
Cytokine
HAT
HDAC
Phosphorylation
SIRT
STAT
Sumoylation
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Summary:Abstract A fascinating question of modern biology is how a limited number of signaling pathways generate biological diversity and crosstalk phenomena in vivo . Well-defined posttranslational modification patterns dictate the functions and interactions of proteins. The signal transducers and activators of transcription (STATs) are physiologically important cytokine-induced transcription factors. They are targeted by a multitude of posttranslational modifications that control and modulate signaling responses and gene expression. Beyond phosphorylation of serine and tyrosine residues, lysine acetylation has recently emerged as a critical modification regulating STAT functions. Interestingly, acetylation can determine STAT signaling codes by various molecular mechanisms, including the modulation of other posttranslational modifications. Here, we provide an overview on the acetylation of STATs and how this protein modification shapes cellular cytokine responses. We summarize recent advances in understanding the impact of STAT acetylation on cell growth, apoptosis, innate immunity, inflammation, and tumorigenesis. Furthermore, we discuss how STAT acetylation can be targeted by small molecules and we consider the possibility that additional molecules controlling STAT signaling are regulated by acetylation. Our review also summarizes evolutionary aspects and we show similarities between the acetylation-dependent control of STATs and other important molecules. We propose the concept that, similar to the ‘histone code’, distinct posttranslational modifications and their crosstalk orchestrate the functions and interactions of STAT proteins.
ISSN:1359-6101
DOI:10.1016/j.cytogfr.2012.06.005