Elucidation of the mechanism for nuclear export of the proteasome

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14958
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SAEKI Yasushi 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, 副参事研究員 (80462779)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 細胞内タンパク質分解 / プロテアソーム / ユビキチン / 細胞質核間輸送 / 質量分析計

Outline of Final Research Achievements

The proteasome mainly localizes in the nucleus in proliferating cells, but it moves to the cytoplasm in human cultured cells stimulated with calcium ionophore and in yeast at stationary phase. Because this nuclear export was not inhibited by leptomycin B, unidentified dedicated exportin for the proteasome might exist in these cells. In this study, we first generated yeast cells that capable of artificially controlling intracellular localization of the proteasome. Then, using the above phenomenon and cells, proteasome interacting proteins were analyzed by a quantitative mass spectrometry. As a result, we identified a number of known and novel proteasome interacting proteins that change upon nuclear export of the proteasome. In addition, we obtained six mutants that are defective in nuclear export of the proteasome. Further analysis of these factors will uncover the molecular mechanism of nucleocytoplasmic transport of the proteasome.

Free Research Field

生化学