Costa S L, McBurney M W
Ottawa Regional Cancer Centre, Department of Biochemsitry, Ontario, Canada.
Exp Cell Res. 1996 May 25;225(1):35-43. doi: 10.1006/excr.1996.0154.
Retinoic acid (RA) is a potent inducer of P19 cell differentiation. RA activity is thought to be mediated by nuclear RA receptors (RARs), transcription factors whose activity is dependent on RA. There are three RARs called alpha, beta, and gamma. We created truncated versions of the three RARs and compared their activities as inhibitors of RA-mediated gene transcription and of P19 cell differentiation. Only mutants of the RAR alpha were inhibitory in these assays. A mutant of RAR alpha carrying a 10-amino-acid insert was able to heterodimerize with RXRbeta or with the normal RAR alpha and the inhibitory activity of this mutant was dependent on an intact DNA binding domain. We conclude that dominant negative mutants of RAR alpha act by heterodimerizing with RXRs or RARs and binding to RA response elements on DNA, thereby preventing binding of the normal receptors to those sites.
视黄酸（RA）是P19细胞分化的有效诱导剂。RA的活性被认为是由核RA受体（RARs）介导的，RARs是一类转录因子，其活性依赖于RA。有三种RARs，分别称为α、β和γ。我们构建了这三种RARs的截短版本，并比较了它们作为RA介导的基因转录和P19细胞分化抑制剂的活性。在这些实验中，只有RARα的突变体具有抑制作用。携带10个氨基酸插入片段的RARα突变体能够与RXRβ或正常的RARα形成异二聚体，并且该突变体的抑制活性依赖于完整的DNA结合结构域。我们得出结论，RARα的显性负突变体通过与RXRs或RARs形成异二聚体并结合到DNA上的RA反应元件来发挥作用，从而阻止正常受体与这些位点的结合。
