Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR
Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR
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DOI：
10.1074/jbc.272.38.23565
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发表时间：
1997-09-19
影响因子：
4.8
通讯作者：
Moore, DD
中科院分区：
文献类型：
--
作者：
Choi, HS;Chung, MR;Moore, DD
我们已经确定了一个新的鼠孤儿成员的核激素受体超家族，称为mCAR，这是密切相关的先前描述的人类孤儿MB 67，这里称为hCAR。与hCAR一样，mCAR表达在肝脏中最高。除了最丰富的mCAR 1同种型外，mCAR基因还表达缺失配体结合/二聚化结构域的C末端部分的截短mCAR 2变体。mCAR基因有8个内含子，这种mCAR 2变体是通过跳过第8个外显子的剪接事件产生的。与hCAR一样，mCAR 1作为异源二聚体与类维生素A X受体结合至来自视黄酸受体β 2同种型启动子的视黄酸应答元件。与其缺乏关键异源二聚化界面一致，mCAR 2变体不结合该位点。mCAR 1和hCAR均明显是组成型转录激活因子，该活性取决于保守的C末端AF-2转录激活基序的存在。正如从其不能结合DNA所预期的，mCAR 2变体既不通过自身反式激活，也不抑制hCAR或mCAR 1的反式激活。
We have identified a new murine orphan member of the nuclear hormone receptor superfamily, termed mCAR, that is closely related to the previously described human orphan MB67, referred to here as hCAR. Like hCAR, mCAR expression is highest in liver, In addition to the most abundant mCAR1 isoform, the mCAR gene expresses a truncated mCAR2 variant that is missing the C-terminal portion of the ligand binding/dimerization domain. The mCAR gene has 8 introns, and this mCAR2 variant is generated by a splicing event that skips the 8th exon. mCAR1, like hCAR, binds as a heterodimer with the retinoid X receptor to the retinoic acid response element from the promoter of the retinoic acid receptor beta 2 isoform, Consistent with its lack of a critical heterodimerization interface, the mCAR2 variant does not bind this site, Both mCAR1 and hCAR are apparently constitutive transcriptional activators, This activity is dependent on the presence of the conserved C terminal AF-2 transcriptional activation motif, As expected from its inability to bind DNA, the mCAR2 variant neither transactivates by itself nor inhibits transactivation by hCAR or mCAR1.