Patho-physiological function of the ubiquitin ligase that generates linear ubiquitin chains (LUBAC)

2016 Fiscal Year Final Research Report

• Project/Area Number: 25253019
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: IWAI Kazuhiro 京都大学, 医学研究科, 教授 (60252459)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ユビキチン / 慢性炎症 / NF-kappaB / 細胞死

Outline of Final Research Achievements

Linear ubiquitin chains and the LUBAC ubiquitin ligase that specifically generate linear chains are involved in NF-kappaB activation and cell death suppression. LUBAC is composed of catalytic HOIP and accessory SHARPIN and HOIL-1L subunits. In this research project, we analyzed functional difference between SHARPIN and HOIL-1L. Although both subunits have NZF domains that can bind to ubiquitin, SHARPIN NZF but not that of HOIL-1L can bind to K63-linked chains. Since LUBAC can be recruited to the activated receptor complex by recognizing K63 chains, loss of SHARPIN attenuated the recruitment of LUBAC to the receptor complex. Then loss of SHARPIN augmented cell death, which leads to the chronic dermatitis that specifically observed in SHARPIN null mice.

Free Research Field

生体分子医学