The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6

J Biol Chem. 2004 Jul 23;279(30):31105-12. doi: 10.1074/jbc.M404428200. Epub 2004 May 15.

Abstract

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.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Cells, Cultured
  • DNA Primers / genetics
  • E1A-Associated p300 Protein
  • Immunoglobulin Heavy Chains / genetics
  • Interleukin-4 / pharmacology
  • Mice
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Coactivator 3
  • Promoter Regions, Genetic
  • Recombinant Proteins / pharmacology
  • STAT6 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Up-Regulation / drug effects

Substances

  • DNA Primers
  • Immunoglobulin Heavy Chains
  • Nuclear Proteins
  • Recombinant Proteins
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Interleukin-4
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • Nuclear Receptor Coactivator 3