Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor gamma (PPARgamma)-interacting protein, is required for PPARgamma-mediated adipogenesis.
Nuclear receptor coactivator PRIP (peroxisome proliferators-activated receptor (PPARgamma)-interacting protein) appears to serve as a linker between cAMP response element-binding protein-binding protein (CBP/p300)anchored and PBP (PPARgamma-binding protein)-anchored coactivator complexes involved in the transcriptional 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 PPARgamma coactivators, suggesting a role for these molecules in PPARgamma-induced adipogenesis. PBP-/- mouse embryonic fibroblasts fail to exhibit PPARgamma-stimulated adipogenesis indicating that PBP is a downstream regulator of PPARgamma-mediated adipogenesis. We now show that PRIP-/- mouse embryonic fibroblasts are also refractory to PPARgamma-stimulated adipogenesis and fail to express adipogenic marker aP2, a PPARgamma-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 PPARgamma-mediated adipogenesis and that both these coactivators are required for the successful completion of adipogenic program.
Qi
Chao
C
Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois 60611-3008, USA.
Surapureddi
Sailesh
S
Zhu
Yi-Jun
YJ
Yu
Songtao
S
Kashireddy
Papreddy
P
Rao
M Sambasiva
MS
Reddy
Janardan K
JK
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D005347:Fibroblasts / Q000378:metabolism; D005822:Genetic Vectors; D005838:Genotype; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D056918:Nuclear Receptor Coactivators; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D002843:Chromatin; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; C405683:Ncoa6 protein, mouse; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse