Arrestin interaction with E3 ubiquitin ligases and deubiquitinases: functional and therapeutic implications.
Arrestin interaction with E3 ubiquitin ligases and deubiquitinases: functional and therapeutic implications.
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DOI：
10.1007/978-3-642-41199-1_10
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发表时间：
2014
影响因子：
--
通讯作者：
S. Shenoy
中科院分区：
文献类型：
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作者：
S. Shenoy
抑制蛋白由四个同源衔接蛋白（抑制蛋白 1-4）组成，最初被鉴定为七次跨膜 G 蛋白偶联受体引发的信号转导抑制剂。目前，已知抑制蛋白（尤其是抑制蛋白 2 和抑制蛋白 3；也称为 β-抑制蛋白 1 和 β-抑制蛋白 2）是细胞信号传导的激活剂和内吞运输的调节剂。抑制蛋白不仅通过与不同的细胞表面受体结合，而且通过与不同细胞内区室中的各种关键信号分子结合来介导这些作用。因此，视紫红质抑制蛋白的功能是多方面的，需要与许多蛋白质相互作用，并且需要一系列选择性构象。此外，通过抑制蛋白特异性诱导信号传导的受体配体正在被发现，并且它们的生理作用正在显现。最近的证据表明，视紫红质抑制蛋白的活性通过其与泛素化途径的特定酶的动态关联而在空间和时间上受到调节。泛素依赖性、抑制蛋白介导的信号传导可以作为开发针对跨膜信号传导和生理反应的新型治疗策略的潜在平台。
Arrestins constitute a small family of four homologous adaptor proteins (arrestins 1–4), which were originally identified as inhibitors of signal transduction elicited by the seven-transmembrane G protein-coupled receptors. Currently arrestins (especially arrestin2 and arrestin3; also called β-arrestin1 and β-arrestin2) are known to be activators of cell signaling and modulators of endocytic trafficking. Arrestins mediate these effects by binding to not only diverse cell-surface receptors but also by associating with a variety of critical signaling molecules in different intracellular compartments. Thus, the functions of arrestins are multifaceted and demand interactions with a host of proteins and require an array of selective conformations. Furthermore, receptor ligands that specifically induce signaling via arrestins are being discovered and their physiological roles are emerging. Recent evidence suggests that the activity of arrestin is regulated in space and time by virtue of its dynamic association with specific enzymes of the ubiquitination pathway. Ubiquitin-dependent, arrestin-mediated signaling could serve as a potential platform for developing novel therapeutic strategies to target transmembrane signaling and physiological responses.