Miyata K S, McCaw S E, Patel H V, Rachubinski R A, Capone J P
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
J Biol Chem. 1996 Apr 19;271(16):9189-92. doi: 10.1074/jbc.271.16.9189.
The yeast two-hybrid system was used to isolate novel cellular factors that interact with the mouse peroxisome proliferator-activated receptor alpha (PPARalpha). One of the interacting clones isolated encoded LXRalpha, a recently described human orphan nuclear hormone receptor. LXRalpha bound directly to PPARalpha, as well as to the common heterodimerization partner 9-cis-retinoic acid receptor (RXRalpha). LXRalpha did not form a DNA binding complex with PPARalpha on synthetic hormone response elements composed of direct repeats of the TGACCT consensus half-site or on naturally occurring peroxisome proliferator response elements (PPREs) or LXRalpha response elements. However, LXRalpha inhibited binding of PPARalpha/RXRalpha heterodimers to PPREs, and coexpression of LXRalpha in mammalian cells antagonized peroxisome proliferator signaling mediated by PPARalpha/RXRalpha in vivo. These findings identify a novel partner for PPARalpha and suggest that LXRalpha plays a role in modulating PPAR-signaling pathways in the cell.
酵母双杂交系统用于分离与小鼠过氧化物酶体增殖物激活受体α（PPARα）相互作用的新型细胞因子。分离得到的一个相互作用克隆编码LXRα，它是最近描述的一种人类孤儿核激素受体。LXRα直接与PPARα以及共同的异源二聚化伴侣9-顺式视黄酸受体（RXRα）结合。在由TGACCT共有半位点直接重复组成的合成激素反应元件上，或在天然存在的过氧化物酶体增殖物反应元件（PPREs）或LXRα反应元件上，LXRα未与PPARα形成DNA结合复合物。然而，LXRα抑制PPARα/RXRα异源二聚体与PPREs的结合，并且在哺乳动物细胞中LXRα的共表达在体内拮抗由PPARα/RXRα介导的过氧化物酶体增殖物信号传导。这些发现确定了PPARα的一个新型伴侣，并表明LXRα在调节细胞内PPAR信号通路中发挥作用。
