Function of ubiquitin-related protein in protein degradation

• Project/Area Number: 14580702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: KOBAYASHI Hideki Kyushu University, Graduate School of Medical Sciences, Assoc.Prof., 大学院・医学研究院, 助教授 (20150394)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Asai A, et al.: "A new structural class of proteasome inhibitors identified by yeast-based assay."Biochem.Pharm.. 67. 227-234 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Asai A et al.: "A new structural class of proteasome inhibitors identified by yeast-based assay."Biochem.Pharm.. 67. 227-234 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
• [Publications] Asai A.et al.: "A new structural class of proteasome inhibitors identified by yeast-based assay."Biochem.Pharm.. 67. 227-234 (2004)
• [Publications] 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)
• [Publications] 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)