| Autor: |
Lieu DJ, Crowder MK, Kryza JR, Tamilselvam B, Kaminski PJ, Kim IJ, Li Y, Jeong E, Enkhbaatar M, Chen H, Son SB, Mok H, Bradley KA, Phillips H, Blanke SR |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 May 23. Date of Electronic Publication: 2024 May 23. |
| DOI: |
10.1101/2024.05.21.595139 |
| Abstrakt: |
Macroautophagy is thought to have a critical role in shaping and refining cellular proteostasis in eukaryotic cells recovering from DNA damage. Here, we report a mechanism by which autophagy is suppressed in cells exposed to bacterial toxin-, chemical-, or radiation-mediated sources of genotoxicity. Autophagy suppression is directly linked to cellular responses to DNA damage, and specifically the stabilization of the tumor suppressor p53, which is both required and sufficient for regulating the ubiquitination and proteasome-dependent reduction in cellular pools of microtubule-associated protein 1 light chain 3 (LC3A/B), a key precursor of autophagosome biogenesis and maturation, in both epithelial cells and an ex vivo organoid model. Our data indicate that suppression of autophagy, through a newly identified p53-proteasome-LC3 axis, is a conserved cellular response to multiple sources of genotoxicity. Such a mechanism could potentially be important for realigning proteostasis in cells undergoing DNA damage repair. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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