The complexity of biological control systems: An autophagy case study.
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Pavel, M., Tanasa, R., Park, S., & Rubinsztein, D. (2022). The complexity of biological control systems: An autophagy case study.. Bioessays, 44 (3) https://doi.org/10.1002/bies.202100224
Funder: UK Dementia Research Institute; Id: http://dx.doi.org/10.13039/501100017510
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.
REVIEW ESSAY, autophagy, cell heterogeneity, mathematical model, precision medicine, transduction pathways, YAP1 signalling
We are grateful for funding from the UK Dementia Research Institute (funded by MRC, Alzheimer’s Research UK and the Alzheimer’s Society), a grant of the Romanian Ministry of Research, Innovation and Digitization, CNCS/CCCDI-UEFISCDI, project number PN-III-P1-1.1-PD-2019-0733, within PNCDI-III, and POC/448/1/1/127606 CENEMED project (M.P.).
Romanian Ministry of Research, Innovation and Digitization, CNCS/CCCDI‐UEFISCDI (PN‐III‐P1‐1.1‐PD‐2019‐0733)
External DOI: https://doi.org/10.1002/bies.202100224
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334371