Function of ubiquitin-related protein in protein degradation

泛素介导的蛋白质降解在真核细胞的许多生物学过程中起着重要作用，包括蛋白质质量控制、细胞周期调控、转录调控和应激反应。被多聚泛素链修饰的蛋白质被19 S调节颗粒捕获，然后被蛋白酶体的20 S核心颗粒降解。与泛素化系统的生物化学和蛋白酶体的分子方面相比，靶蛋白如何被递送到蛋白酶体并被蛋白酶体识别还不完全清楚。在这项研究中，我们表明，UbL-UBA结构域蛋白Dsk 2在酵母中是一个衔接蛋白，有助于提供多泛素化蛋白的蛋白酶体。Dsk 2的C-末端乌巴结构域与多聚泛素链结合，其N-末端UbL结构域与19 S调节颗粒的Rpn 1受体结合。我们还发现，Sem 1，Dsk 2介导的抑制因子之一，是蛋白体RP的一个组成部分。Sem 1似乎在蛋白酶体中19 S RP-20 S CP相互作用的稳定性和组装中起调节剂的作用。

Ubiquitin-mediated protein degradation plays a vital role in many eukaryotic celluler processes including protein quality control, cell cycle control, transcription regulation and stress responses. Proteins modified by polyubiquitin chains are captured by the 19S regulatory particle and then degraded by the 20S core particle of the proteasome. Compared with the well-understood biochemistry of the ubiquitnation system and the molecular aspects of the proteasome, it is not completely clear yet how targeted proteins are delivered to and recognized by the proteasome. In this research, we show that the UbL-UBA domain protein Dsk2 in yeast is one of adaptor proteins that help to deliver polyubiquitinated proteins to the proteasome. The C-terminal UBA domain of Dsk2 binds to polyubiquitin chains and its N-terminal UbL domain binds to the Rpn1 receptor of the 19S regulatory particle. We also find that Sem1, one of the Dsk2-mediated suppressor, is a component of the proteaosomal RP. Sem1 seems to function as a regulator in the stability and assembly of the 19S RP-20S CP interaction in the proteasome.