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  4. Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk
 
research article

Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk

Petherick, Katy J.
•
Williams, Ann C.
•
Lane, Jon D.
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2013
The EMBO Journal

The Wnt/β-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/β-catenin signalling pathway as a negative regulator of both basal and stress-induced autophagy. Manipulation of β-catenin expression levels in vitro and in vivo revealed that β-catenin suppresses autophagosome formation and directly represses p62/SQSTM1(encoding the autophagy adaptor p62) via TCF4. Furthermore, we show that during nutrient deprivation β-catenin is selectively degraded via the formation of a β-catenin-LC3 complex, attenuating β-catenin/TCF-driven transcription and proliferation to favour adaptation during metabolic stress. Formation of the β-catenin-LC3 complex is mediated by a W/YXXI/L motif and LC3-interacting region (LIR) in β-catenin, which is required for interaction with LC3 and non-proteasomal degradation of β-catenin. Thus, Wnt/β-catenin represses autophagy and p62 expression, while β-catenin is itself targeted for autophagic clearance in autolysosomes upon autophagy induction. These findings reveal a regulatory feedback mechanism that place β-catenin at a key cellular integration point coordinating proliferation with autophagy, with implications for targeting these pathways for cancer therapy.

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Type
research article
DOI
10.1038/emboj.2013.123
Web of Science ID

WOS:000321331900012

Author(s)
Petherick, Katy J.
Williams, Ann C.
Lane, Jon D.
Ordóñez-Morán, Paloma
Huelsken, Joerg  orcid-logo
Collard, Tracey J.
Smartt, Helena Jm
Batson, Jennifer
Malik, Karim
Paraskeva, Chris
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Date Issued

2013

Publisher

Nature Publishing Group

Published in
The EMBO Journal
Volume

32

Issue

13

Start page

1903

End page

1916

Subjects

autophagy

•

cancer

•

LC3

•

p62

•

Wnt/beta-catenin

Editorial or Peer reviewed

NON-REVIEWED

Written at

EPFL

EPFL units
UPHUELSKEN  
Available on Infoscience
July 2, 2013
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/93180
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