Willy P J, Umesono K, Ong E S, Evans R M, Heyman R A, Mangelsdorf D J
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas 75235-9050, USA.
Genes Dev. 1995 May 1;9(9):1033-45. doi: 10.1101/gad.9.9.1033.
We have identified a new retinoid response pathway through which 9-cis retinoic acid (9cRA) activates transcription in the presence of LXR alpha, a member of the nuclear receptor superfamily. LXR alpha shows a specific pattern of expression in visceral organs, thereby restricting the response to certain tissues. Retinoid trans-activation occurs selectively on a distinct response element termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXR alpha in mediating this retinoid response. We provide evidence that the retinoid response on the LXRE is the result of a unique interaction between LXR alpha and endogenous RXR, which, unlike in the RXR/RAR heterodimer, makes RXR competent to respond to retinoids. Thus, the interaction with LXR alpha shifts RXR from its role described previously as a silent, DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXREs.
我们已经确定了一条新的类视黄醇反应途径，通过该途径，9-顺式视黄酸（9cRA）在核受体超家族成员LXRα存在的情况下激活转录。LXRα在内脏器官中呈现出特定的表达模式，从而将反应限制在某些组织中。类视黄醇反式激活选择性地发生在一个称为LXRE的独特反应元件上。值得注意的是，无论是RXR同二聚体还是RXR/RAR异二聚体都不能在介导这种类视黄醇反应中替代LXRα。我们提供的证据表明，LXRE上的类视黄醇反应是LXRα与内源性RXR之间独特相互作用的结果，与RXR/RAR异二聚体不同，这使得RXR能够对类视黄醇作出反应。因此，与LXRα的相互作用使RXR从其先前被描述为沉默的DNA结合伙伴的角色转变为通过LXRE定义的靶基因介导类视黄醇反应的活性配体结合亚基。
