Function of ubiquitin-associated domain proteins for decoding polyubiquitin signaling.

2016 Fiscal Year Final Research Report

• Project Area: New aspect of the ubiquitin system : its enormous roles in protein regulation
• Project/Area Number: 24112007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Metropolitan University
• Principal Investigator: Hiroyuki Kawahara 首都大学東京, 理工学研究科, 教授 (70291151)
• Co-Investigator(Kenkyū-buntansha): 横田 直人 首都大学東京, 理工学研究科, 助教 (40610564)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: ユビキチン / プロテアソーム / タンパク質の品質管理 / 膜タンパク質 / BAG6 / UBQLN4 / UBAドメイン / ポリユビキチン認識

Outline of Final Research Achievements

Most of transmembrane proteins are integrated into the ER by virtue of a signal sequence-mediated co-translational process. However, a substantial portion of transmembrane proteins fail to access the ER, resulting in the production of cytosolically mislocalized polypeptides. Their appropriate recognition and removal are of the utmost significance to avoid potential proteotoxic stress. Here, we identified UBA domain protein UBQLN4 for the elimination of such newly synthesized defective polypeptides. Using a model transmembrane domain protein whose degradation occurs at a pre-ER incorporation process, we show that UBQLN4 recognizes misassembled proteins in the cytoplasm for targeting to the proteasome pathway. Importantly, UBQLN4 recognized not only the model defective transmembrane substrate but also a pool of endogenous defective proteins that were induced by compromising the signal recognition particle.

Free Research Field

生化学　細胞生物学