Ser727-dependent transcriptional activation by association of p300 with STAT3 upon IL-6 stimulation.
Activation of the signal transducer and activator of transcription 3 (STAT3) in response to interleukin-6 (IL-6) type cytokines involves both phosphorylation of Tyr705, which enables dimerization, nuclear translocation and DNA binding, as well as ser727 phosphorylation. Here, we describe that the 65 C-terminal amino acids of STAT3 can function as an independent transcription activation domain (TAD), particularly when a negative charge is introduced at position 727 by mutation of the serine residue into aspartate. The strong transcriptional activity of the C-terminal STAT3 Ser727Asp TAD is coupled to a constitutive association with the co-activator p300. In HepG2 cells, p300 associates with STAT3 upon IL-6 stimulation, and overexpression of p300 enhances the transcriptional activity of STAT3alpha, but not of STAT3beta or STAT3 Ser727Ala. We conclude that Ser727 phosphorylation in the C-terminal region of STAT3 is required for transactivation by association with p300.
Schuringa
J J
JJ
Department of Genetics, Biological Center, Kerlaan 30, 9751 NN Haren, The Netherlands.
Schepers
H
H
Vellenga
E
E
Kruijer
W
W
D019943:Amino Acid Substitution; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D050796:STAT3 Transcription Factor; D012694:Serine / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D012694:Serine