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α-Catenin levels determine direction of YAP/TAZ response to autophagy perturbation

Published version
Peer-reviewed

Change log

Authors

Park, So Jung 
Frake, Rebecca A. 
Son, Sung Min 
Manni, Marco M. 

Abstract

Abstract: The factors regulating cellular identity are critical for understanding the transition from health to disease and responses to therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptional regulators of the Hippo pathway via unrelated mechanisms. Here, we confirm that autophagy perturbation in different cell types can cause opposite responses in growth-promoting oncogenic YAP/TAZ transcriptional signalling. These apparently contradictory responses can be resolved by a feedback loop where autophagy negatively regulates the levels of α-catenins, LC3-interacting proteins that inhibit YAP/TAZ, which, in turn, positively regulate autophagy. High basal levels of α-catenins enable autophagy induction to positively regulate YAP/TAZ, while low α-catenins cause YAP/TAZ activation upon autophagy inhibition. These data reveal how feedback loops enable post-transcriptional determination of cell identity and how levels of a single intermediary protein can dictate the direction of response to external or internal perturbations.

Description

Funder: UK Dementia Research Institute

Keywords

Article, /631/80, /631/80/39, /631/80/39/2346, /13, /13/1, /13/89, /13/106, /14, /14/19, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

12

Publisher

Nature Publishing Group UK