A NOVEL PATHWAY FOR VITAMIN-A SIGNALING MEDIATED BY RXR HETERODIMERIZATION WITH NGFI-B AND NURR1
A NOVEL PATHWAY FOR VITAMIN-A SIGNALING MEDIATED BY RXR HETERODIMERIZATION WITH NGFI-B AND NURR1
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DOI：
10.1101/gad.9.7.769
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发表时间：
1995-04-01
影响因子：
10.5
通讯作者：
JANSSON, L
中科院分区：
文献类型：
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作者：
PERLMANN, T;JANSSON, L
除了作为 9-顺式视黄酸受体的作用外，RXR 通过与核受体的异二聚化在多种激素途径的调节中具有重要作用。在这里，我们发现两个孤儿受体 NGFI-B 和 NURR1 先前已被证明可以作为单体与 DNA 相互作用，也可以与 RXR 形成异二聚体。这些异二聚体选择性地结合一类由 5 个核苷酸间隔的同向重复序列组成的视黄酸反应元件。在这方面，它们类似于 RXR 和全反式视黄酸受体 RAR 之间形成的异二聚体。然而，虽然 RXR 在 RXR-RAR 异二聚体中受到抑制，但 NGFI-B/NURR1 促进响应 RXR 配体的有效激活，因此将 RXR 从沉默转变为活跃的异二聚体伙伴。这些数据表明，NGFI-B 和 NURR1 可以通过允许一类不同的直接重复序列充当特定的 RXR 响应元件，从而增加 RXR 以配体依赖性方式调节基因表达的潜力。由于 NGFI-B 和 NURR1 的表达均由各种生长因子快速诱导，因此这些发现还表明了维生素 A 或类视黄醇与生长因子信号通路之间收敛的新机制。
In addition to its role as a 9-cis retinoic acid receptor, RXR has an important role in the regulation of multiple hormonal pathways through heterodimerization with nuclear receptors. Here, we show that two orphan receptors, NGFI-B and NURR1, which have been shown previously to interact with DNA as monomers, also can heterodimerize with RXR. These heterodimers bind selectively to a class of retinoic acid response elements composed of direct repeats spaced by 5 nucleotides. In this respect they are similar to heterodimers formed between RXR and the receptor for all-trans retinoic acid, RAR. However, whereas RXR is inhibited in the RXR-RAR heterodimer, NGFI-B/NURR1 promote efficient activation in response to RXR ligands and therefore shift RXR from a silent to an active heterodimerization partner. These data show that NGFI-B and NURR1 can increase the potential of RXR to modulate gene expression in a ligand-dependent manner by allowing a distinct class of direct repeats to serve as specific RXR response elements. Because expression of both NGFI-B and NURR1 is rapidly induced by various growth factors, these findings also suggest a novel mechanism for convergence between vitamin A or retinoid and growth factor signaling pathways.