Cellular Physiology and Biochemistry | |
GABARAPL1 Negatively Regulates Wnt/β-catenin Signaling by Mediating Dvl2 Degradation through the Autophagy Pathway | |
关键词: Wnt signaling; GABARAPL1; Autophagy; Dvl2; | |
DOI : 10.1159/000329952 | |
学科分类:分子生物学,细胞生物学和基因 | |
来源: S Karger AG | |
【 摘 要 】
Wnt signaling is critical for many biological processes and is tightly regulated. In this study, we found that GABARAPL1 (GABAA receptor-associated protein like 1, GABARAPL1) interacts with Dvl2 by both yeast two-hybrid screening and immunoprecipitation experiments. Furthermore, we observed that p62 is required for the interaction of Dvl2 and GABARAPL1. Luciferase assays indicated that GABARAPL1 represses Wnt/β-catenin signaling stimulated by Wnt1, Dvl2 and β-catenin. We further demonstrated that GABARAPL1 mediates degradation of Dvl2 and the effect is blocked by addition of 3-MA, a specific inhibitor of autophagy. Finally, we provided evidence that over-expression of GABARAPL1 inhibits proliferation and tumor growth of MCF7 cells in vitro and in nude mice. Taken together, our results suggested that GABARAPL1 as a tumor repressor inhibits Wnt signaling via mediating Dvl2 degradation through the autophagy pathway.
【 授权许可】
CC BY-NC-ND
【 预 览 】
Files | Size | Format | View |
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RO201904032328999ZK.pdf | 575KB | download |