The role of SUMO modifications on estrogen receptor function by kinase signaling pathways

最近，SUMO化的鉴定，SUMO，一个小的泛素样修饰剂，共价连接到靶蛋白的过程，已经成为一种新的蛋白质修饰，调节越来越多的转录因子的功能。SUMO化的功能后果在分子水平上还不清楚，但最近的观察表明，核受体被报道为SUMO化，这提出了一个有趣的可能性，即SUMO化可能作为一种新的机制，通过这种机制，激素信号通路可能调节transcription.Our的专业知识，在核受体的研究主要来自我们的工作雌激素受体ER a和ER b。随着ERb的鉴定，我们对ER激活途径的重新评估已经允许认识到ER a和ER b选择性地受EGF家族的生长因子调节，EGF家族的生长因子指导ER磷酸化，因此提供了ER进行翻译后修饰的潜力。这些研究揭示了非激素介导的途径如何通过雌激素受体调节转录的新方面。随着越来越多的证据表明SUMO化代表了ER功能中尚未受到广泛关注的新机制，并且基于磷酸化和SUMO化密切相关的概念来调节转录因子，这些研究旨在确定雌激素受体的这两种多位点翻译后修饰之间的功能偶联，以整合它们的转录能力和细胞功能。

Recently, the identification of SUMOylation, the process by which SUMO, a small ubiquitin-like modifier, is covalently linked to target proteins, has emerged as a new protein modification that regulates the function of an increasing number of transcription factors. The functional consequences of SUMOylation are not understood at the molecular level, but with recent observations that nuclear receptors were reported to be SUMOylated, this raises the interesting possibility that SUMOylation may serve as a novel mechanism by which hormonal signaling pathways may regulate transcription.Our expertise in the study of nuclear receptors has mainly arise from our work on estrogen receptors ERa and ERb. With the identification of ERb, our reevaluation of ER activation pathways has allowed to recognize that ERa and ERb are selectively regulated by growth factors of the EGF family which direct ER phosphorylation, therefore providing a potential of ERs to undergo posttranslational modifications. These studies therefore uncover novel aspects on how non hormonal mediated pathways may regulate transcription by estrogen receptors.With the emerging evidence that SUMOylation represents a novel mechanism in ER functions that has not received widespread attention, and based on the rising concept that phosphorylation and SUMOylation are intimately associated to regulate transcription factors, these studies aim at defining a functional coupling between these two multisite posttranslational modifications of estrogen receptors to integrate their transcriptional competence and cellular functions.