p300 interacts with the N- and C-terminal part of PPARγ2 in a ligand-independent and -dependent manner, respectively
p300 interacts with the N- and C-terminal part of PPARγ2 in a ligand-independent and -dependent manner, respectively
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DOI：
10.1074/jbc.274.12.7681
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发表时间：
1999-03-19
影响因子：
4.8
通讯作者：
Auwerx, J
中科院分区：
文献类型：
--
作者：
Gelman, L;Zhou, GC;Auwerx, J
核过氧化物酶体增殖物激活受体γ (PPAR γ)激活参与细胞内和细胞外脂质代谢的多种基因的转录。一些辅助因子对核受体转录活性的刺激或沉默至关重要。两个同源的辅助因子p300和creb结合蛋白（CBP）已被证明共同激活几种核受体的配体依赖性转录活性以及雄激素受体的配体非依赖性转录活性。这里显示p300 / CBP之间的交互和PPARγ在每个蛋白质很复杂,涉及多个领域,p300 / CBP不仅ligand-dependent方式绑定到PPARγDEF地区还将ligand-independent方式直接绑定到一个区域在AB域之间的局部残留31到99年,在转染实验,p300 / CBP从而增强转录活动的激活函数(AF) 1和AF-2域。p300/CBP在其N端（CBP的残基1和113之间）和蛋白质中间（残基1099和1460之间）显示出至少两个PPAR γ的对接位点。
The nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) activates the transcription of multiple genes involved in intra- and extracellular lipid metabolism. Several cofactors are crucial for the stimulation or the silencing of nuclear receptor transcriptional activities. The two homologous cofactors p300 and CREB-binding protein (CBP) have been shown to co-activate the ligand-dependent transcriptional activities of several nuclear receptors as well as the ligand-independent transcriptional activity of the androgen receptor. We show here that the interaction between p300/CBP and PPAR gamma is complex and involves multiple domains in each protein, p300/CBP not only bind in a ligand-dependent manner to the DEF region of PPAR gamma but also bind directly in a ligand-independent manner to a region in the AB domain localized between residue 31 to 99, In transfection experiments, p300/CBP could thereby enhance the transcriptional activities of both the activating function (AF)-1 and AF-2 domains. p300/CBP displays itself at least two docking sites for PPAR gamma located in its N terminus (between residues 1 and 113 for CBP) and in the middle of the protein (between residues 1099 and 1460).