Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy.
Adv Exp Med Biol. 2010;693:54-66. doi: 10.1007/978-1-4419-7005-3_4.
STAR (Signal Transduction and Activation of RNA) proteins owed their name to the presence in their structure ofa RNA-binding domain and several hallmarks of their involvement in signal transduction pathways. In many members of the family, the STAR RNA-binding domain (also named GSG, an acronym for GRP33/Sam68/ GLD-1) is flanked by regulatory regions containing proline-rich sequences, which serve as docking sites for proteins containing SH3 and WW domains and also a tyrosine-rich region at the C-terminus, which can mediateprotein-protein interactions with partners through SH2 domains. These regulatory regions contain consensus sequences for additional modifications, including serine/threonine phosphorylation, methylation, acetylation and sumoylation. Since their initial description, evidence has been gathered in different cell types and model organisms that STAR proteins can indeed integrate signals from external and internal cues with changes in transcription and processing of target RNAs. The most striking example of the high versatility of STAR proteins is provided by Sam68 (KHDRBS1), whose function, subcellular localization and affinity for RNA are strongly modulated by several signaling pathways through specific modifications. Moreover, the recent development of genetic knockout models has unveiled the physiological function of some STAR proteins, pointing to a crucial role of their post-translational modifications in the biological processes regulated by these RNA-binding proteins. This chapter offers an overview of the most updated literature on the regulation of STAR proteins by post-translational modifications and illustrates examples of how signal transduction pathways can modulate their activity and affect biological processes.
STAR（信号转导和 RNA 激活）蛋白因其结构中存在 RNA 结合域和几个参与信号转导途径的特征而得名。在该家族的许多成员中，STAR RNA 结合域（也称为 GSG，GRP33/Sam68/GLD-1 的缩写）被包含脯氨酸丰富序列的调节区域所包围，这些序列作为含有 SH3 和 WW 结构域的蛋白质的 docking 位点，并且 C 末端富含酪氨酸区域，可通过 SH2 结构域与伴侣蛋白进行蛋白质-蛋白质相互作用。这些调节区域包含用于其他修饰的共识序列，包括丝氨酸/苏氨酸磷酸化、甲基化、乙酰化和 SUMO 化。自最初描述以来，在不同的细胞类型和模式生物中已经收集到证据，表明 STAR 蛋白确实可以整合来自外部和内部线索的信号，并改变靶 RNA 的转录和加工。STAR 蛋白高度多功能性的最显著例子是 Sam68（KHDRBS1），其功能、亚细胞定位和与 RNA 的亲和力通过几种信号通路通过特定修饰得到强烈调节。此外，遗传敲除模型的最新发展揭示了一些 STAR 蛋白的生理功能，表明其翻译后修饰在这些 RNA 结合蛋白调节的生物过程中起着关键作用。本章概述了关于 STAR 蛋白翻译后修饰调节的最新文献，并举例说明了信号转导途径如何调节它们的活性并影响生物过程。
