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 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.
Krämer
Oliver H
OH
Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine (CMB), University of Jena, Hans-Knöll-Str. 2, 07743 Jena, Germany. Oliver.Kraemer@uni-jena.de
Heinzel
Thorsten
T
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D005973:Glutamine; D007372:Interferons; D001120:Arginine; D006655:Histone Deacetylases; D008239:Lysine