Cheng Minzhang, Xue Hua, Cao Weipeng, Li Wenxia, Chen Hua, Liu Bofeng, Ma Benyu, Yan Xiaohua, Chen Ye-Guang
From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
J Biol Chem. 2016 Jun 10;291(24):12871-12879. doi: 10.1074/jbc.M115.708818. Epub 2016 Apr 20.
Wnt signaling plays a critical role in embryonic development, tissue homeostasis, and cancer development. Dishevelled (Dvl) is an essential and central component in Wnt signaling, and its stability and activity is tightly regulated. It has been shown that Dvl can be degraded via both the proteasome and autophagy-lysosome pathways. Here we report that receptor for activated C kinase 1 (RACK1) negatively regulates Dishevelled stability and Wnt signaling. RACK1 interacts with Dvl proteins and promotes their lysosomal degradation, and this effect is enhanced by autophagy induction. RACK1 also interacts with LC3 and enhances the association of LC3 with Dvl2, thereby leading to degradation of Dvl proteins through autophagy. These findings reveal a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability.
Wnt信号通路在胚胎发育、组织稳态和癌症发展中起着关键作用。Dishevelled（Dvl）是Wnt信号通路中一个必不可少的核心成分，其稳定性和活性受到严格调控。研究表明，Dvl可通过蛋白酶体和自噬-溶酶体途径降解。在此，我们报告活化C激酶1受体（RACK1）负向调节Dishevelled的稳定性和Wnt信号通路。RACK1与Dvl蛋白相互作用并促进其溶酶体降解，自噬诱导可增强这种作用。RACK1还与LC3相互作用并增强LC3与Dvl2的结合，从而通过自噬导致Dvl蛋白降解。这些发现揭示了RACK1通过调节Dvl稳定性在Wnt信号通路中的一种新的调节功能。
