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J Biol Chem. 2013 Feb 8;288(6):3753-67. doi: 10.1074/jbc.M112.415240. Epub 2012 Dec 31.

HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction.

Author information

1
Department of Cancer Targets, Genentech Inc., South San Francisco, California 94080, USA. tran.hoanh@gene.com

Abstract

The adenomatous polyposis coli (APC) protein functions 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 Lys-48-linked polyubiquitylation and proteasomal degradation. APC is conjugated with Lys-63-linked 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 Lys-63 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.

PMID:
23277359
PMCID:
PMC3567630
DOI:
10.1074/jbc.M112.415240
[Indexed for MEDLINE]
Free PMC Article

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