Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor γ (PPARγ)-interacting protein, is required for PPARγ- mediated adipogenesis
Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor γ (PPARγ)-interacting protein, is required for PPARγ- mediated adipogenesis
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DOI：
10.1074/jbc.c300175200
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发表时间：
2003-07-11
影响因子：
4.8
通讯作者：
Reddy, JK
中科院分区：
文献类型：
--
作者：
Qi, C;Surapureddi, S;Reddy, JK
核受体共激活因子 PRIP（过氧化物酶体增殖物激活受体 (PPARgamma) 相互作用蛋白）似乎充当 cAMP 反应元件结合蛋白结合蛋白 (CBP/p300) 锚定和 PBP（PPARgamma 结合蛋白）锚定共激活因子复合物之间的连接物，参与核受体的转录活性。 PRIP 和 PBP 基因的破坏会导致胚胎第 11.5 天至 12.5 天（交配后）之间的胚胎致死，表明 PRIP 和 PBP 是必需且非冗余的共激活剂。 PRIP 和 PBP 最初被鉴定为 PPARgamma 共激活剂，表明这些分子在 PPARgamma 诱导的脂肪形成中发挥作用。 PBP-/- 小鼠胚胎成纤维细胞未能表现出 PPARγ 刺激的脂肪生成，表明 PBP 是 PPARγ 介导的脂肪生成的下游调节剂。我们现在发现 PRIP-/- 小鼠胚胎成纤维细胞对 PPARγ 刺激的脂肪生成也具有抵抗力，并且不能表达脂肪生成标记物 aP2（一种 PPARγ 响应基因）。染色质免疫沉淀分析显示 PRIP-/- 细胞中 PIMT（PRIP 结合蛋白）和 PBP 与 aP2 基因启动子的关联减少，表明 PRIP 是 CBP/p300 锚定辅因子复合物与 PBP 锚定介体复合物连接所必需的。这些数据表明 PRIP 与 PBP 一样，是 PPARgamma 介导的脂肪生成的下游调节剂，并且这两种共激活剂都是成功完成脂肪生成程序所必需的。
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.