Tran H, Bustos D, Yeh R, Rubinfeld B, Lam C, Shriver S, Zilberleyb I, Lee MW, Phu L, Sarkar AA, Zohn IE, Wertz IE, Kirkpatrick DS, Polakis P

The adenomatous polyposis coli (APC) protein function as a negative regulator of the Wnt signaling pathway. In this capacity, APC forms a 'destruction complex' with Axin, CK1α and GSK3β to foster phosphorylation of the Wnt effector β-catenin earmarking it for K48-linked polyubiquitylation and proteasomal degradation. APC is conjugated with K63-linked ...

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ubiquitin chains when it is bound to Axin, but it is unclear whether this modification promotes the APC-Axin interaction or confers upon APC an alternative function in the destruction complex. Here we identify HectD1 as a candidate E3 ubiquitin ligase that modifies APC with K63-polyubiquitin. Knockdown of HectD1 diminished APC ubiquitylation, disrupted the APC-Axin interaction, and augmented Wnt3a-induced β-catenin stabilization and signaling. These results indicate that HectD1 promotes the APC-Axin interaction to negatively regulate Wnt signaling.

Date: Dec. 31, 2012

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