Transcriptional activation by STAT6 requires the direct interaction with NCoA-1.
Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that is activated by interleukin-4 (IL-4)-induced tyrosine phosphorylation and mediates most of the IL-4-induced gene expression. Transcriptional activation by STAT6 requires the interaction with coactivators like p300 and the CREB-binding protein (CBP). In this study we have investigated the function of the CBP-associated members of the p160/steroid receptor coactivator family in the transcriptional activation by STAT6. We found that only one of them, NCoA-1, acts as a coactivator for STAT6 and interacts directly with the transactivation domain of STAT6. The N-terminal part of NCoA-1 interacts with the far C-terminal part of the STAT6 transactivation domain but does not interact with the other members of the STAT family. This domain of NCoA-1 has a strong inhibitory effect on STAT6-mediated transactivation when overexpressed in cells, illustrating the importance of NCoA-1 for STAT6-mediated transactivation. In addition, we showed that both coactivators CBP and NCoA-1 bind independently to specific regions within the STAT6 transactivation domain. Our results suggest that multiple contacts between NCoA-1, CBP, and STAT6 are required for transcriptional activation. These findings provide new mechanistic insights into how STAT6 can recruit coactivators required for IL-4-dependent transactivation.
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Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Strasse 42-44, 60596 Frankfurt, Germany.
Pfitzner
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D000596:Amino Acids / Q000378:metabolism; D002460:Cell Line; D051548:Histone Acetyltransferases; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology; D056920:Nuclear Receptor Coactivator 1; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000502:physiology; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D000596:Amino Acids; D018168:Receptors, Retinoic Acid; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1