The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6.
Transcriptional activation by signal transducer and activator of transcription 6 (STAT6) has been shown to require the direct interaction not only with co-activators such as p300 and cAMP-responsive element-binding protein-binding protein (CBP) but also with nuclear co-activator 1, a member of the p160/steroid receptor co-activator family. Among the p160/steroid receptor co-activators, only p/CIP (nuclear co-activator 3) has been shown to be up-regulated by interleukin (IL)-4 in B cells through a STAT-6-dependent mechanism using Gene-Chip analysis. In this study, we have investigated the function of p/CIP in the transcriptional activation by STAT6. We found that p/CIP indirectly interacted with STAT6 via p300, and overexpression of the CBP-interacting domain of p/CIP (p/CIP(947-1084)) prevented the interaction of p/CIP with STAT6 by blocking the binding of p/CIP to p300. Whereas expression of p/CIP(947-1084) resulted in a marked reduction of STAT6-mediated transactivation, overexpression of wild type p/CIP resulted in significant enhancement of it. In addition, p/CIP(947-1084) markedly reduced CD23 expression on B cells stimulated with IL-4, whereas overexpression of wild type p/CIP enhanced it. Chromatin immunoprecipitations demonstrate that IL-4 increases the interaction of p/CIP with the murine immunoglobulin heavy chain germ line epsilon promoter in B cells. These results suggest that p/CIP positively regulates STAT6 transcriptional activation through formation of a STAT6, p300/CBP, and p/CIP complex.
Arimura
Akinori
A
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
vn Peer
Maartje
M
Schröder
Andreas J
AJ
Rothman
Paul B
PB
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D050881:E1A-Associated p300 Protein; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000494:pharmacology; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D056921:Nuclear Receptor Coactivator 3