Ser727-dependent Transcriptional Activation by Association of p300 With STAT3 Upon IL-6 Stimulation

FEBS Lett. 2001 Apr 20;495(1-2):71-6. doi: 10.1016/s0014-5793(01)02354-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Interleukin-6 / pharmacology*
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / metabolism*
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Protein Structure, Tertiary / physiology
  • STAT3 Transcription Factor
  • Serine / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation / drug effects*
  • Transcriptional Activation / physiology

Substances

  • DNA-Binding Proteins
  • Interleukin-6
  • Nuclear Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Serine