Regulation of ubiquitin homeostasis at endosomes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26440070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Shizuoka University
• Principal Investigator: Kimura Yoko 静岡大学, 農学部, 教授 (80291152)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ユビキチン / ホメオスタシス / エンドソーム / タンパク質分解 / 脱ユビキチン化酵素 / Rfu1 / Bro1 / 熱ストレス

Outline of Final Research Achievements

Yeast Rfu1 (Regulator for free ubiquitin chain 1) localizes to endosomes and plays a role in ubiquitin homeostasis by inhibiting the activity of Doa4.We showed that Bro1, a class E vacuolar protein sorting protein that recruits Doa4 to endosomes, also recruits Rfu1 to endosomes by the direct interaction between a region containing the YPEL motif in Rfu1 and the V domain in Bro1, which could be analogous to the interaction between the mammalian Alix V domain and YPXnL motifs of target proteins. Overexpression of Bro1 and the V domain prevented Rfu1 degradation after heat shock. Rfu1 degradation partly involved the proteasome and Rsp5.Finally, we showed that Rim20, another yeast Bro1 family protein, binds to Rim101 through the interaction between the V domain and the YPIKL motif. These results suggest that interactions between V domains and YP(X)nL motifs are conserved from yeast to mammalian cells. We also showed the specificities of each V domain to their target protein.

Free Research Field

分子細胞生物学