Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2M9.
PPAR Res. 2009;2009:925309. doi: 10.1155/2009/925309. Epub 2009 Dec 20.
The PPARs are integral parts of the RXR-dependent signaling networks. Many other nuclear receptor subfamily 1 members also require RXR as their obligatory heterodimerization partner and they are often co-expressed in any given tissue. Therefore, the PPARs often complete with other RXR-dependent nuclear receptors and this competition has important biological implications. Thorough understanding of this cross-talk at the molecular level is crucial to determine the detailed functional roles of the PPARs. At the level of DNA binding, most RXR heterodimers bind selectively to the well-known "DR1 to 5" DNA response elements. As a result, many heterodimers share the same DR element and must complete with each other for DNA binding. At the level of heterodimerization, the partners of RXR share the same RXR dimerization interface. As a result, individual nuclear receptors must complete with each other for RXR to form functional heterodimers. Cross-talk through DNA binding and RXR heterodimerization present challenges to the study of these nuclear receptors that cannot be adequately addressed by current experimental approaches. Novel tools, such as engineered nuclear receptors with altered dimerization properties, are currently being developed. These tools will enable future studies to dissect specific RXR heterodimers and their signaling pathways.
PPAR 是 RXR 依赖性信号网络的组成部分。许多其他核受体亚家族 1 成员也需要 RXR 作为其必需的异二聚体化伙伴，并且它们通常在任何给定的组织中共同表达。因此，PPAR 通常与其他 RXR 依赖性核受体竞争，这种竞争具有重要的生物学意义。在分子水平上彻底理解这种串扰对于确定 PPAR 的详细功能作用至关重要。在 DNA 结合水平上，大多数 RXR 异二聚体选择性地结合到众所周知的“DR1 到 5”DNA 反应元件。因此，许多异二聚体共享相同的 DR 元件，必须相互竞争以进行 DNA 结合。在异二聚化水平上，RXR 的伴侣共享相同的 RXR 二聚化界面。因此，单个核受体必须相互竞争以形成功能性异二聚体。通过 DNA 结合和 RXR 异二聚化的串扰给这些核受体的研究带来了挑战，当前的实验方法无法充分解决这些挑战。目前正在开发具有改变的二聚化特性的工程核受体等新型工具。这些工具将使未来的研究能够剖析特定的 RXR 异二聚体及其信号通路。
