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α-Catenin Levels Determine Direction of YAP/TAZ Response to Autophagy Perturbation

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pavel, Mariana 
Park, So Jung 
Frake, Rebecca 
Son, Sung Min 

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 report that autophagy perturbation in different cell types can have 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, which 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

Keywords

Adaptor Proteins, Signal Transducing, Animals, Autophagy, Cells, Cultured, Epithelial Cells, Feedback, Physiological, Humans, Mice, Microtubule-Associated Proteins, Mutation, Protein Binding, Protein Interaction Domains and Motifs, Signal Transduction, Trans-Activators, Transcription Factors, Transcriptional Coactivator with PDZ-Binding Motif Proteins, YAP-Signaling Proteins, alpha Catenin

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

Publisher

Nature Research
Sponsorship
Wellcome Trust (095317/Z/11/Z)
Wellcome Trust (100140/Z/12/Z)
This work was supported by the UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society) (DCR) and The Roger de Spoelberch Foundation (DCR), a Romanian grant of Ministery of Research and Innovation CNCS–UEFISCDI, project number PN-III-P1-1.1-PD-2019-0733, within PNCDI III (MP) and L'Oréal-UNESCO For Women in Science Awards Programme (MP).