Jj. Schuringa et al., Ser727-dependent transcriptional activation by association of p300 with STAT3 upon IL-6 stimulation, FEBS LETTER, 495(1-2), 2001, pp. 71-76
Activation of the signal transducer and activator of transcription 3 (STAT3
) in response to interleukin-6 (IL-6) type cytokines involves both phosphor
ylation of Tyr705, which enables dimerization, nuclear translocation and DN
A binding, as well as ser727 phosphorylation, Here, we describe that the 65
C-terminal amino acids of STAT3 can function as an independent transcripti
on activation domain (TAD), particularly when a negative charge is introduc
ed at position 727 by mutation of the serine residue into aspartate, The st
rong transcriptional activity of the C-terminal STAT3 Ser727Asp TAD is coup
led to a constitutive association with the co-activator p300, In HepG2 cell
s, p300 associates with STAT3 upon IL-6 stimulation, and overexpression of
p300 enhances the transcriptional activity of STAT3 alpha, but not of STAT3
beta or STAT3 Ser727Ala. We conclude that Ser727 phosphorylation in the C-
terminal region of STAT3 is required for transactivation by association wit
h p300, (C) 2001 Federation of European Biochemical Societies. Published by
Elsevier Science B,V. All rights reserved.