Roles of BAG6 complex in nuclear protein quality contorol

2014 Fiscal Year Final Research Report

• Project/Area Number: 25840038
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan University
• Principal Investigator: YOKOTA Naoto 首都大学東京, 理工学研究科, 助教 (40610564)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: BAG6 / 不良タンパク質 / 核内凝集体

Outline of Final Research Achievements

The protein quality control system plays a pivotal role in proteostasis in cells. Although it was reported that BAG6 is involved in recognition and degradation of misfolded newly synthesized proteins, and biogenesis of a group of transmembrane protein that does not have a signal sequence at its N-terminus, the precise roles of BAG6 in these processes and in the nucleus have not been elucidated yet.
I attempted to clarify roles of BAG6 and its cofactors such as TRC35, TRC40 and Ubl4a in the nucleus and revealed that TRC35 and dimerization of TRC40 are responsible for interaction between BAG6 and TRC40. In order to analyze the mechanism of misfolded protein degradation in the nucleus, we produced a model substrate conjugated a nuclear localization signal. We observed that degradation of the substrates abolished in the presence of proteasomal inhibitor but not in the presence of leptomycin.

Free Research Field

細胞生化学