Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor γ (PPARγ)-interacting protein, is required for PPARγ-mediated adipogenesis

Chao Qi, Sailesh Surapureddi, Yi Jun Zhu, Songtao Yu, Papreddy Kashireddy, M. Sambasiva Rao, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Nuclear receptor coactivator PRIP (peroxisome proliferators-activated receptor (PPAR-γ)-interacting protein) appears to serve as a linker between cAMP response element-binding protein-binding protein (CBP/ p300)anchored and PBP (PPAR-γ-binding protein)-anchored coactivator complexes involved in the transcrip. tional activity of nuclear receptors. Disruption of PRIP and PBP genes results in embryonic lethality between embryonic day 11.5 and 12.5 (postcoitum), indicating that PRIP and PBP are essential and nonredundant coactivators. Both PRIP and PBP were initially identified as PPARγ coactivators, suggesting a role for these molecules in PPARγ-induced adipogenesis. PBP-/- mouse embryonic fibroblasts fail to exhibit PPARγ-stimulated adipogenesis indicating that PBP is a downstream regulator of PPARγ-mediated adipogenesis. We now show that PRIP-/- mouse embryonic fibroblasts are also refractory to PPARγ-stimulated adipogenesis and fail to express adipogenic marker aP2, a PPARγ-responsive gene. Chromatin immunoprecipitation assays reveal reduced association in PRIP-/- cells of PIMT (PRIP-binding protein) and PBP with aP2 gene promoter, suggesting that PRIP is required for the linking of CBP/p300-anchored cofactor complex with PBP-anchored mediator complex. These data indicate that PRIP, like PBP, is a downstream regulator of PPARγ-mediated adipogenesis and that both these coactivators are required for the successful completion of adipogenic program.

Original languageEnglish (US)
Pages (from-to)25281-25284
Number of pages4
JournalJournal of Biological Chemistry
Volume278
Issue number28
DOIs
StatePublished - Jul 11 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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