Cm. Litterst et E. Pfitzner, Transcriptional activation by STAT6 requires the direct interaction with NCoA-1, J BIOL CHEM, 276(49), 2001, pp. 45713-45721
Signal transducer and activator of transcription 6 (STAT6) is a transcripti
on factor that is activated by interleukin-4 (IL-4)-induced tyrosine phosph
orylation and mediates most of the IL-4-induced gene expression. Transcript
ional activation by STAT6 requires the interaction with coactivators like p
300 and the CREB-binding protein (CBP). In this study we have investigated
the function of the CBP-associated members of the p160/ steroid receptor co
activator family in the transcriptional activation by STAT6. We found that
only one of them, NCoA-1, acts as a coactivator for STAT6 and interacts dir
ectly with the transactivation domain of STAT6. The N-terminal part of NCoA
-1 interacts with the far C-terminal part of the STAT6 transactivation doma
in but does not interact with the other members of the STAT family. This do
main of NCoA-1 has a strong inhibitory effect on STAT6-mediated transactiva
tion when overexpressed in cells, illustrating the importance of NCoA-1 for
STAT6-mediated transactivation. In addition, we showed that both coactivat
ors 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 f
indings provide new mechanistic insights into how STAT6 can recruit coactiv
ators required for IL-4-dependent transactivation.