Cell type-specific YAP1-WWTR1/TAZ transcriptional responses after autophagy perturbations are determined by levels of α-catenins (CTNNA1 and CTNNA3). Issue 7 (3rd July 2021)

• Record Type: Journal Article
• Authors: Pavel, Mariana; Park, So Jung; Tanasa, Radu; Rubinsztein, David C.
• Is Part Of: Autophagy. Volume 17:Issue 7(2021)
• Page Start: 1788
• Page End: 1790
• Publication Date: 2021-07-03
• Subjects: α-catenin -- autophagy -- Hippo signaling -- mathematical model -- YAP1-WWTR1/TAZ; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2021.1934273
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: The YAP1-WWTR1/TAZ transcription co-factors are key determinants of cell growth that are perturbed in many cancers. Previous studies have reported divergent responses in YAP1-WWTR1/TAZ activities after autophagy perturbations in different contexts. Recently, we identified that α-catenin levels determine whether YAP1-WWTR1/TAZ signaling will be increased or decreased after macroautophagy/autophagy inhibition/induction. CTNNA1/α-catenin can act as a switch in this pathway, as it is an autophagy substrate and a negative regulator of YAP1-WWTR1/TAZ. However, YAP1-WWTR1/TAZ are also directly degraded by autophagy and there is a feedback loop where YAP1-WWTR1/TAZ positively regulate autophagy. These features were integrated into a mathematical numerical model based on a set of differential equations in order to clarify the integrated output on YAP1-WWTR1/TAZ activity at different time-points after autophagy perturbation in cells with distinct initial levels of α-catenins (CTNNA1 and CTNNA3). Our theoretical and experimental data allow an understanding of cell-type specific and time-dependent responses to autophagy manipulations that may be relevant in many contexts, including different types of cancer.