Analysis of interaction with synthesis and degradation in linear ubiquitin mediated NF-kappaB activation.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860188
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Nakagawa Tomoko 京都大学, 医学(系)研究科(研究院), 研究員 (90623976)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: シグナル伝達 / NF-kappaB / ユビキチン

Outline of Final Research Achievements

I have shown that OTULIN and CYLD, which are deubiquitinating enzymes (DUBs) cleaving linear ubiquitin chains specifically, down-regulate NF-κB activation by binding to HOIP, a subunit of LUBAC. Based on my original findings, I dissected the physiological roles of coordinated synthesis and cleavage of linear ubiquitination by co-existing its ligase and DUBs in this research proposal. Using OTULIN conditional knockout mice, I have dissected the roles of coordinated synthesis and cleavage of linear ubiquitination in B and T lymphocytes. To my disappointment, I could not found any abnormality in OTULIN null T or B cells. However, in collaboration with the research group in Hokkaido University, I start dissecting the molecular mechanisms underlying hyper-inflammatory symptoms found in a patient having mutations in OTULIN genes and found that inflammation provoked by pathogens could not be terminated because of the attenuated DUB activity of OTULIN.

Free Research Field

分子生物学