The complexity of biological control systems: An autophagy case study. (14th January 2022)

• Record Type: Journal Article
• Authors: Pavel, Mariana; Tanasa, Radu; Park, So Jung; Rubinsztein, David C.
• Is Part Of: BioEssays. Volume 44:Number 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-14
• Subjects: autophagy -- cell heterogeneity -- mathematical model -- precision medicine -- transduction pathways -- YAP1 signalling; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202100224
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Autophagy and YAP1‐WWTR1/TAZ signalling are tightly linked in a complex control system of forward and feedback pathways which determine different cellular outcomes in differing cell types at different time‐points after perturbations. Here we extend our previous experimental and modelling approaches to consider two possibilities. First, we have performed additional mathematical modelling to explore how the autophagy‐YAP1 crosstalk may be controlled by posttranslational modifications of components of the pathways. Second, since analogous contrasting results have also been reported for autophagy as a regulator of other transduction pathways engaged in tumorigenesis (Wnt/β‐catenin, TGF‐β/Smads, NF‐kB or XIAP/cIAPs), we have considered if such discrepancies may be explicable through situations involving competing pathways and feedback loops in different cell types, analogous to the autophagy‐YAP/TAZ situation. Since distinct posttranslational modifications dominate those pathways in distinct cells, these need to be understood to enable appropriate cell type‐specific therapeutic strategies for cancers and other diseases. Abstract : External and internal perturbations of autophagy initiate a dynamic control system, defined by positive and negative forward and feedback paths, to regulate the activity of various transduction pathways (e.g., YAP1, Wnt/β‐catenin, TGF‐β/Smads, NF‐kB or XIAP/cIAPs signallings).