In:
Science, American Association for the Advancement of Science (AAAS), Vol. 364, No. 6440 ( 2019-05-10)
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.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.aau0812
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2019
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11