Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion.
Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion.
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DOI：
10.1038/s41598-017-03783-w
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Gupta A
中科院分区：
文献类型：
--
作者：
Bakshi K;Ranjitha B;Dubey S;Jagannadham J;Jaiswal B;Gupta A
PXR 是核受体超家族的成员，也是一种特征明确的外源代谢介质。 PXR 激活的经典模式涉及其与适当配体的结合以及随后与其伙伴 RXR 的异二聚化。然而，翻译后修饰和与不同细胞因子的串扰等各种因素也可能调节 PXR 的功能动力学和行为。在本研究中，我们发现 TIP60（一种必需的赖氨酸乙酰转移酶蛋白）与未配体的 PXR 相互作用，并且该复合物共同促进细胞迁移和粘附。 TIP60 利用其 NR Box 与 PXR 的 LBD 区域相互作用，并在赖氨酸 170 处乙酰化 PXR，以诱导其核内重组。此外，TIP60-PXR 复合物的形成不需要 RXR，并且该复合物不会诱导配体依赖性 PXR 靶基因反式激活。有趣的是，我们观察到 PXR 增强了 TIP60 对组蛋白的催化活性。这是第一份证明 TIP60 与 PXR 独特相互作用的报告，并揭示了 TIP60-PXR 复合物在细胞迁移和粘附中的潜在作用。
PXR is a member of nuclear receptor superfamily and a well-characterized mediator of xenobiotic metabolism. The classical mode of PXR activation involves its binding to appropriate ligand and subsequent heterodimerization with its partner RXR. However, various factors such as post-translational modifications and crosstalk with different cellular factors may also regulate the functional dynamics and behavior of PXR. In the present study, we have identified that TIP60, an essential lysine acetyltransferase protein interacts with unliganded PXR and together this complex promotes cell migration & adhesion. TIP60 utilizes its NR Box to interact with LBD region of PXR and acetylates PXR at lysine 170 to induce its intranuclear reorganization. Also, RXR is not required for TIP60-PXR complex formation and this complex does not induce ligand-dependent PXR target gene transactivation. Interestingly, we observed that PXR augments the catalytic activity of TIP60 for histones. This is the first report demonstrating the exclusive interaction of TIP60 with PXR and uncovers a potential role for the TIP60-PXR complex in cell migration and adhesion.