NDLI: HectD1 E3 Ligase Modifies Adenomatous Polyposis Coli (APC) with Polyubiquitin to Promote the APC-Axin Interaction

Content Provider	Journal of Biological Chemistry (JBC)
Author	Tran, Hoanh Bustos, Daisy Yeh, Ronald Rubinfeld, Bonnee Lam, Cynthia Shriver, Stephanie Zilberleyb, Inna Lee, Michelle W. Phu, Lilian Sarkar, Anjali A. Zohn, Irene E. Wertz, Ingrid E. Kirkpatrick, Donald S. Polakis, Paul
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.
Related Links	http://www.jbc.org/content/288/6/3753.abstract
Ending Page	3767
Starting Page	3753
Page Count	15
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	6
Volume Number	288
DOI	10.1074/jbc.M112.415240
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2013-02-08
Access Restriction	Open
Subject Keyword	Deubiquitylation Signal Transduction Tumor Suppressor Gene Ubiquitin Ligase Ubiquitylation Β-Catenin Destruction Complex APC Axin HectD1 E3 Ligase Lys-63-linked Ubiquitin Chains Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Reversible Modification of Adenomatous Polyposis Coli (APC) with K63-linked Polyubiquitin Regulates the Assembly and Activity of the β-Catenin Destruction Complex

HectD1 E3 Ligase Modifies Adenomatous Polyposis Coli (APC) with Polyubiquitin to Promote the APC-Axin Interaction

HectD1 E3 Ligase Modifies Adenomatous Polyposis Coli (APC) with Polyubiquitin to Promote the APC-Axin Interaction

Reversible Modification of Adenomatous Polyposis Coli (APC) with K63-linked Polyubiquitin Regulates the Assembly and Activity of the β-Catenin Destruction Complex

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HectD1 E3 Ligase Modifies Adenomatous Polyposis Coli (APC) with Polyubiquitin to Promote the APC-Axin Interaction

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