Wnt pathway activation by ADP-ribosylation.
Wnt pathway activation by ADP-ribosylation.
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DOI：
10.1038/ncomms11430
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发表时间：
2016-05-03
影响因子：
16.6
通讯作者：
Ahmed Y
中科院分区：
文献类型：
--
作者：
Yang E;Tacchelly-Benites O;Wang Z;Randall MP;Tian A;Benchabane H;Freemantle S;Pikielny C;Tolwinski NS;Lee E;Ahmed Y
Wnt/β-catenin signalling directs fundamental processes during metazoan development and can be aberrantly activated in cancer. Wnt stimulation induces the recruitment of the scaffold protein Axin from an inhibitory destruction complex to a stimulatory signalosome. Here we analyse the early effects of Wnt on Axin and find that the ADP-ribose polymerase Tankyrase (Tnks)—known to target Axin for proteolysis—regulates Axin's rapid transition following Wnt stimulation. We demonstrate that the pool of ADP-ribosylated Axin, which is degraded under basal conditions, increases immediately following Wnt stimulation in both Drosophila and human cells. ADP-ribosylation of Axin enhances its interaction with the Wnt co-receptor LRP6, an essential step in signalosome assembly. We suggest that in addition to controlling Axin levels, Tnks-dependent ADP-ribosylation promotes the reprogramming of Axin following Wnt stimulation; and propose that Tnks inhibition blocks Wnt signalling not only by increasing destruction complex activity, but also by impeding signalosome assembly. Wnt/β-catenin signalling directs several developmental processes and is aberrantly activated in several cancers. Here the authors implicate Tankyrase—previously shown to target the scaffolding protein Axin for proteolysis—in early Wnt signalling by promoting the interaction between Axin and the Wnt co-receptor LRP6.
