Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites.
Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites.
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从内部蛋白质翻译起始位点表达的人类组成型雄甾烷受体变体对 DR-1 PPRE 的反式激活。
DOI：
10.1093/nar/gkm090
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发表时间：
2007
影响因子：
14.9
通讯作者：
Omiecinski,CurtisJ
中科院分区：
文献类型：
--
作者：
Stoner,MatthewA;Auerbach,ScottS;Zamule,StephanieM;Strom,StephenC;Omiecinski,CurtisJ
Downstream in-frame start codons produce amino-terminal-truncated human constitutive androstane receptor protein isoforms (ΔNCARs). The ΔNCARs are expressed in liver andin vitrocell systems following translation from in-frame methionine AUG start codons at positions 76, 80, 125, 128, 168 and 265 within the full-length CAR mRNA. The resulting CAR proteins lack the N-terminal DNA-binding domain (DBD) of the receptor, yielding ΔNCAR variants with unique biological function. Although the ΔNCARs maintain full retinoid X receptor alpha (RXRα) heterodimerization capacity, the ΔNCARs are inactive on classical CAR-inducible direct repeat (DR)-4 elements, yet efficiently transactivate a DR-1 element derived from the endogenous PPAR-inducible acyl-CoA oxidase gene promoter. RXRαheterodimerization with CAR1, CAR76 and CAR80 isoforms is necessary for the DR-1 PPRE activation, a function that exhibits absolute dependence on both the respective RXRαDBD and CAR activation (AF)-2 domains, but not the AF-1 or AF-2 domain of RXRα, nor CAR's DBD. A new model of CAR DBD-independent transactivation is proposed, such that in the context of a DR-1 peroxisome proliferator-activated response element, only the RXRαportion of the CAR-RXRαheterodimer binds directly to DNA, with the AF-2 domain of tethered CAR mediating transcriptional activation of the receptor complex.
