Ser727‐dependent transcriptional activation by association of p300 with STAT3 upon IL‐6 stimulation

FEBS Letters

Kruijer, Wiebe¹  Schuringa, Jan-Jacob¹  Vellenga, Edo²  Schepers, Hein¹ 

[1] Department of Genetics, Biological Center, Kerklaan 30, 9751 NN Haren, The Netherlands;Department of Hematology, University Hospital Groningen, 9700 RB Groningen, The Netherlands

关键词: Interleukin-6;    Signal transducer and activator of transcription 3;    Ser727 phosphorylation;    Transactivation;    p300;    IL-6;    interleukin-6;    STAT3;    signal transducer and activator of transcription 3;    TAD;    transcription activation domain;    CBP;    CREB binding protein;   

DOI  :  10.1016/S0014-5793(01)02354-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 STAT3α, but not of STAT3β or STAT3 Ser727Ala. We conclude that Ser727 phosphorylation in the C-terminal region of STAT3 is required for transactivation by association with p300.

【 授权许可】

Unknown