The molecular mechanism regulating ubiquitination of aberrant plasma membrane protein

2014 Fiscal Year Final Research Report

• Project/Area Number: 25893275
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kwansei Gakuin University
• Principal Investigator: OKIYONEDA Tsukasa 関西学院大学, 理工学部, 准教授 (90398248)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Keywords: 脱ユビキチン化 / CFTR / タンパク質品質管理

Outline of Final Research Achievements

Here, we sought to identify the deubiquitination enzyme (DUB) involved in the peripheral protein quality control mechanism that eliminates aberrant plasma membrane proteins such as ΔF508 CFTR. Analysis of a panel of DUB inhibitors discovered that inhibition of proteasome-associated DUB increased the cell surface expression and stability of ΔF508 CFTR. Moreover, endocytosis of ΔF508 CFTR was dramatically inhibited by inhibitors of proteasome-associated DUB. These results provide a novel regulatory mechanism that the proteasome-associated deubiquitination stimulates the elimination of aberrant plasma membrane proteins from the cell surface.

Free Research Field

タンパク質品質管理