Molecular mechanism for activation of RBR-type E3 ubiquitin ligases

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18545
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: YAMANO Koji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (30547526)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ユビキチン / RBR型リガーゼ / ミトコンドリア / マイトファジー

Outline of Final Research Achievements

E3 ligases transfer ubiquitin molecules to substrate proteins for their degradation. Molecular functions of RBR-type E3 ligases, however, largely remain unknown because their activities normally keep autoinhibited. Parkin is one of the RBR type E3 ligase that activates only on the dysfunctional mitochondria. In this study, I developed a method in which Parkin activation can be monitored in cultured cells through the interaction of E2 enzymes. E2 enzymes play a role in transferring ubiquitin molecule to E3 ligases and 40 different E2 enzymes are encoded in human genome. Using the method, I identified several E2 enzymes to interact with activated Parkin on the damaged mitochondria. Furthermore, this method also identified that one of the uncharacterized RBR-type E3 ligase forms several dot-like structures in the nucleus, and another RBR-type E3 ligase localizes on the lipid droplets.

Free Research Field

分子細胞生物学