Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling
Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling
复制标题
活化 C 激酶 1 (RACK1) 的受体通过自噬促进蓬乱蛋白降解并拮抗 Wnt 信号转导
DOI：
10.1074/jbc.m115.708818
复制
发表时间：
2016-06-10
影响因子：
4.8
通讯作者：
Chen, Ye-Guang
中科院分区：
文献类型：
--
作者：
Cheng, Minzhang;Xue, Hua;Chen, Ye-Guang
WNT信号在胚胎发育、组织动态平衡和癌症发展中起着关键作用。Disheveled(DVL)是Wnt信号的重要组成部分，其稳定性和活性受到严格调控。已有研究表明，DVL可通过蛋白酶体和自噬-溶酶体途径降解。在这里，我们报告激活的C激酶1受体(RACK1)负向调节蓬乱的稳定性和Wnt信号。RACK1与DVL蛋白相互作用，促进其溶酶体降解，并通过自噬诱导增强这种作用。RACK1还与Lc3相互作用，增强Lc3与Dvl2的结合，从而通过自噬导致DVL蛋白的降解。这些发现揭示了RACK1通过调节DVL稳定性在Wnt信号中的一种新的调节功能。
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.