Function of ubiquitin-related protein in protein degradation

泛素相关蛋白在蛋白质降解中的作用

• 批准号: 14580702
• 负责人: KOBAYASHI Hideki
• 金额: $ 2.3万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580702/
• 关键词: proteolysis; ubiquitin-related protein; proteasome; ubiquitin chain; UBA domain; UbL domain; 蛋白質分解; ユビキチン; 細胞周期; サイクリン

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.

泛素介导的蛋白质降解在许多真核细胞过程中发挥着至关重要的作用，包括蛋白质质量控​​制、细胞周期控制、转录调节和应激反应。多聚泛素链修饰的蛋白质被19S调节颗粒捕获，然后被蛋白酶体的20S核心颗粒降解。与广为人知的泛素化系统的生物化学和蛋白酶体的分子方面相比，目前尚不完全清楚靶向蛋白质是如何传递到蛋白酶体并被蛋白酶体识别的。在这项研究中，我们证明酵母中的 UbL-UBA 结构域蛋白 Dsk2 是有助于将多泛素化蛋白递送至蛋白酶体的接头蛋白之一。 Dsk2 的 C 端 UBA 结构域与多聚泛素链结合，其 N 端 UbL 结构域与 19S 调节颗粒的 Rpn1 受体结合。我们还发现 Sem1（Dsk2 介导的抑制因子之一）是蛋白酶体 RP 的组成部分。 Sem1 似乎在蛋白酶体中 19S RP-20S CP 相互作用的稳定性和组装中发挥调节作用。

项目成果

M.Funakoshi et al.: "Budding yeast Dsk2p is a polyubiquitin-binding protein that can interact with the proteasome"Proc.Natl.Acad.Sci.USA.. 99. 745-750 (2002)

M.Funakoshi 等人：“芽殖酵母 Dsk2p 是一种多聚泛素结合蛋白，可以与蛋白酶体相互作用”Proc.Natl.Acad.Sci.USA.. 99. 745-750 (2002)

T.Goda et al.: "The RRASK motif in Xenopus cyclin B2 is required for the substrate recognition of Cdc25C by the cyclin B-cdc2 complex"J.Biol.Chem.. 278(In press). (2003)

T.Goda 等人：“爪蟾细胞周期蛋白 B2 中的 RRASK 基序是细胞周期蛋白 B-cdc2 复合物对 Cdc25C 的底物识别所必需的”J.Biol.Chem.. 278（正在出版）。

Goda T, et al.: "The RRASK motif in Xenopus cyclin B2 is required for the substrate recognition of Cdc25C by the cyclin B-cdc2 complex."J.Biol.Chem.. 278. 19032-19037 (2003)

Goda T 等人：“爪蟾细胞周期蛋白 B2 中的 RRASK 基序是细胞周期蛋白 B-cdc2 复合物对 Cdc25C 的底物识别所必需的。”J.Biol.Chem.. 278. 19032-19037 (2003)

Asai A, et al.: "A new structural class of proteasome inhibitors identified by yeast-based assay."Biochem.Pharm.. 67. 227-234 (2004)

Asai A 等人：“通过基于酵母的测定鉴定出一类新结构的蛋白酶体抑制剂。”Biochem.Pharm.. 67. 227-234 (2004)

Funakoshi M, et al.: "Budding yeast Dsk2p is a polyubiquitin-binding protein that can interact with the proteasome."Proc.Natl.Acad.Sci.USA.. 99. 745-750 (2002)

Funakoshi M 等人：“芽殖酵母 Dsk2p 是一种多聚泛素结合蛋白，可以与蛋白酶体相互作用。”Proc.Natl.Acad.Sci.USA.. 99. 745-750 (2002)