| Literature DB >> 31073040 |
Jin Huk Choi1, Xue Zhong1, William McAlpine1, Tzu-Chieh Liao1, Duanwu Zhang1, Beibei Fang1, Jamie Russell1, Sara Ludwig1, Evan Nair-Gill1, Zhao Zhang1, Kuan-Wen Wang1, Takuma Misawa1, Xiaoming Zhan1, Mihwa Choi1, Tao Wang1,2, Xiaohong Li1, Miao Tang1, Qihua Sun1, Liyang Yu1, Anne R Murray1, Eva Marie Y Moresco1, Bruce Beutler3.
Abstract
Precise control of Wnt signaling is necessary for immune system development. In this study, we detected severely impaired development of all lymphoid lineages in mice, resulting from an N-ethyl-N-nitrosourea-induced mutation in the limb region 1-like gene (Lmbr1l), which encodes a membrane-spanning protein with no previously described function in immunity. The interaction of LMBR1L with glycoprotein 78 (GP78) and ubiquitin-associated domain-containing protein 2 (UBAC2) attenuated Wnt signaling in lymphocytes by preventing the maturation of FZD6 and LRP6 through ubiquitination within the endoplasmic reticulum and by stabilizing "destruction complex" proteins. LMBR1L-deficient T cells exhibited hallmarks of Wnt/β-catenin activation and underwent apoptotic cell death in response to proliferative stimuli. LMBR1L has an essential function during lymphopoiesis and lymphoid activation, acting as a negative regulator of the Wnt/β-catenin pathway.Entities:
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Year: 2019 PMID： 31073040 PMCID： PMC7206793 DOI： 10.1126/science.aau0812
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714