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

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Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk. / Petherick, Katy J; Williams, Ann C; Lane, Jon D; Ordóñez-Morán, Paloma; Huelsken, Joerg; Collard, Tracey J; Smartt, Helena Jm; Batson, Jennifer; Malik, Karim; Paraskeva, Christos; Greenhough, Alexander.

In: EMBO Journal, Vol. 32, No. 13, 04.06.2013, p. 1903 - 1916.

Research output: Contribution to journalArticle

Harvard

Petherick, KJ, Williams, AC, Lane, JD, Ordóñez-Morán, P, Huelsken, J, Collard, TJ, Smartt, HJ, Batson, J, Malik, K, Paraskeva, C & Greenhough, A 2013, 'Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk' EMBO Journal, vol. 32, no. 13, pp. 1903 - 1916. https://doi.org/10.1038/emboj.2013.123

APA

Petherick, K. J., Williams, A. C., Lane, J. D., Ordóñez-Morán, P., Huelsken, J., Collard, T. J., ... Greenhough, A. (2013). Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk. EMBO Journal, 32(13), 1903 - 1916. https://doi.org/10.1038/emboj.2013.123

Vancouver

Petherick KJ, Williams AC, Lane JD, Ordóñez-Morán P, Huelsken J, Collard TJ et al. Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk. EMBO Journal. 2013 Jun 4;32(13):1903 - 1916. https://doi.org/10.1038/emboj.2013.123

Author

Petherick, Katy J ; Williams, Ann C ; Lane, Jon D ; Ordóñez-Morán, Paloma ; Huelsken, Joerg ; Collard, Tracey J ; Smartt, Helena Jm ; Batson, Jennifer ; Malik, Karim ; Paraskeva, Christos ; Greenhough, Alexander. / Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk. In: EMBO Journal. 2013 ; Vol. 32, No. 13. pp. 1903 - 1916.

Bibtex

@article{e3ef78903c8347d6b89590214b5cbd9b,
title = "Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk",
abstract = "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.",
author = "Petherick, {Katy J} and Williams, {Ann C} and Lane, {Jon D} and Paloma Ord{\'o}{\~n}ez-Mor{\'a}n and Joerg Huelsken and Collard, {Tracey J} and Smartt, {Helena Jm} and Jennifer Batson and Karim Malik and Christos Paraskeva and Alexander Greenhough",
year = "2013",
month = "6",
day = "4",
doi = "10.1038/emboj.2013.123",
language = "English",
volume = "32",
pages = "1903 -- 1916",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "13",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk

AU - Petherick, Katy J

AU - Williams, Ann C

AU - Lane, Jon D

AU - Ordóñez-Morán, Paloma

AU - Huelsken, Joerg

AU - Collard, Tracey J

AU - Smartt, Helena Jm

AU - Batson, Jennifer

AU - Malik, Karim

AU - Paraskeva, Christos

AU - Greenhough, Alexander

PY - 2013/6/4

Y1 - 2013/6/4

N2 - 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.

AB - 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.

U2 - 10.1038/emboj.2013.123

DO - 10.1038/emboj.2013.123

M3 - Article

VL - 32

SP - 1903

EP - 1916

JO - EMBO Journal

T2 - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 13

ER -