Phosphorylation–acetylation switch in the regulation of STAT1 signaling

STAT1 signaling regulates the expression of important genes controlling cell growth, differentiation, apoptosis, and immune functions. Biochemical and genetic experiments have identified how this cascade is modulated. Phosphorylation of STAT1 tyrosine and serine moieties is induced rapidly by cytoki...

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Published in:Molecular and cellular endocrinology 2010-02, Vol.315 (1), p.40-48
Main Authors: Krämer, Oliver H., Heinzel, Thorsten
Format: Article
Language:English
Subjects:
Acetylation
Amino Acid Sequence
Animals
Arginine - chemistry
Arginine - metabolism
Gene Expression
Glutamine - chemistry
Glutamine - metabolism
Histone deacetylase
Histone Deacetylases - metabolism
Interferon
Interferons - metabolism
Lysine - chemistry
Lysine - metabolism
Phosphorylation
Protein Processing, Post-Translational
Signal Transduction - physiology
STAT1
STAT1 Transcription Factor - genetics
STAT1 Transcription Factor - metabolism
STAT2
STAT3
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
TCP45
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Summary:STAT1 signaling regulates the expression of important genes controlling cell growth, differentiation, apoptosis, and immune functions. Biochemical and genetic experiments have identified how this cascade is modulated. Phosphorylation of STAT1 tyrosine and serine moieties is induced rapidly by cytokines and growth factors. Upon nuclear translocation, phosphorylated STAT1 homo- and heterodimers activate gene expression. Inactivation of phosphorylated nuclear STAT1 has to be precisely regulated in order to allow signal transduction within limited time frames. Lysine acetylation has recently been appreciated as a novel mechanism regulating signal transduction events relying on STAT proteins. Here, we review these analyses and the finding that a switch from phosphorylated to acetylated STAT1 regulates acetylation-dependent dephosphorylation of STAT1 via the T cell tyrosine phosphatase. We discuss how these observations can be integrated into our current understanding of STAT-dependent cytokine signaling and its potential relevance for endocrine functions.
ISSN:0303-7207
1872-8057
0303-7207
DOI:10.1016/j.mce.2009.10.007