Elucidation of the mechanism for the proteasome assembly regulated by

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: The University of Tokyo
• Principal Investigator: Yashiroda Hideki 東京大学, 大学院薬学系研究科(薬学部), 准教授 (20311425)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: プロテアソーム / リボソーム

Outline of Final Research Achievements

TIF6 was isolated as a gene related to the ubiquitin-proteasome system (UPS) in S. cerevisiae. TIF6 (translation initiation factor 6) is an essential gene, and encodes one of the chaperone proteins involved in the biogenesis of the 60S ribosome. DAmP (decreased abundance by mRNA perturbation) mutant cells of Tif6 showed three phenotypes, all of which indicate the relation between Tif6 and the UPS. 1) tif6-DAmP cells are sensitive to the amino acid analogs. 2) The model substrates of the 26S proteasome are not efficiently degraded in the tif6-DAmP mutant. 3) Double mutations of TIF6 and the proteasome genes cause synthetic growth defects. Tif6 is a highly conserved among eukaryotes, and its human ortholog is eIF6 (>70% identity). Thus, we next investigated the relation between eIF6 and the UPS. Knockdown of eIF6 led to retardation of the assembly of proteasomes, and yeast two-hybrid assays indicated that eIF6 interacts with some proteasome subunits.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

細胞内における選択的なタンパク質分解のためのマシナリーであるプロテアソームとタンパク質合成のためのマシナリーであるリボソームとがTif6/eIF6を介して関連している可能性を示唆した。Tif6/eIF6は60Sリボソームの形成に関わるシャペロンであると同時に、80Sリボソーム形成においてチェックポイント機能を果たす分子でもあることが知られていた。Tif6/eIF6の発現減弱細胞はさらにプロテアソーム形成にも異常を示し、またプロテアソームサブユニットとも相互作用することが今回明らかとなり、タンパク質合成とタンパク質分解が協調している可能性を示した。