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2016 ; 7
(ä): 11430
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Wnt pathway activation by ADP-ribosylation
#MMPMID27138857
Yang E
; Tacchelly-Benites O
; Wang Z
; Randall MP
; Tian A
; Benchabane H
; Freemantle S
; Pikielny C
; Tolwinski NS
; Lee E
; Ahmed Y
Nat Commun
2016[May]; 7
(ä): 11430
PMID27138857
show ga
Wnt/?-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.
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