| First Author | Choi JH | Year | 2019 |
| Journal | Science | Volume | 364 |
| Issue | 6440 | PubMed ID | 31073040 |
| Mgi Jnum | J:274568 | Mgi Id | MGI:6303730 |
| Doi | 10.1126/science.aau0812 | Citation | Choi JH, et al. (2019) LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling. Science 364(6440) |
| abstractText | 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/beta-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/beta-catenin pathway. |
