Differential roles of C-terminal activation motifs in the establishment of Stat6 transcriptional specificity.

Goenka S, Marlar C, Schindler U, Boothby M
J Biol Chem. 2003 278 (50): 50362-70

PMID: 14519766 · DOI:10.1074/jbc.M305854200

Members of the Stat transcription factor family are specifically activated by cytokines, and each Stat mediates its biological effects through the trans-activation of a unique profile of target genes. This specificity is achieved even when Stat proteins mediating opposite transcriptional effects bind to the same palindromic Stat sites in target genes. We show here that the non-conserved sequences of Stat transcription activation domains (TADs) contribute to specificity in promoter activation. Chimeric proteins in which the Stat6 TAD was replaced by that from Stat1alpha or Stat5 exhibited normal interleukin-4-inducible DNA binding activity, but at best modest trans-activation of reporters containing Stat6 binding sites, and a failure to activate the endogenous CD23 promoter in primary B cells. The p160 coactivator nuclear coactivator-1 (Src-1) was specifically recruited by and coactivated Stat6 but not the chimeric Stat6 molecules. Strikingly, transcriptional responses exhibited distinct requirements for the nuclear coactivator-1 interaction motif of the Stat6 C terminus. Together, these findings indicate that the Stat6 TAD contributes to promoter specificity by the differential recruitment of and requirement for a p160-class coactivator.

MeSH Terms (28)

Amino Acid Motifs Amino Acids Cell Line DNA, Complementary DNA-Binding Proteins Histone Acetyltransferases Humans Immunoblotting Interleukin-4 Milk Proteins Nuclear Proteins Nuclear Receptor Coactivator 1 Plasmids Precipitin Tests Promoter Regions, Genetic Protein Binding Protein Structure, Tertiary Receptors, IgE Recombinant Fusion Proteins Retroviridae STAT1 Transcription Factor STAT5 Transcription Factor STAT6 Transcription Factor Trans-Activators Transcription, Genetic Transcriptional Activation Transcription Factors Transfection

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