The phosphatidylinositol 3-kinase vacuolar protein sorting 34 (Vps34) promotes autophagy and receptor endocytosis and degradation. Xiao et al. observed a negative correlation between levels of the SCF ubiquitin ligase component FBXL20 (a p53-activated gene) and levels of Vps34 and autophagy. Following p53 activation by DNA damage, FBXL20 mRNA levels and SCF-mediated Vps34 ubiquitination and degradation increased, and autophagy decreased; DNA damage-induced phosphorylation of Vps34 increased Vps34–FBXL20 binding. Furthermore, FBXL20 knockdown and p53 activation resulted in an increase and decrease in Vps34-mediated epidermal growth factor receptor (EGFR) degradation, respectively. Thus, p53 activation by DNA damage results in FBXL20 upregulation and increased Vps34 degradation, and inhibits autophagy and receptor degradation.
References
Xiao, J. et al. FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation. Genes Dev. http://dx.doi.org/10.1101/gad.252528.114 (2015)
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Zlotorynski, E. p53-controlled autophagy. Nat Rev Mol Cell Biol 16, 68 (2015). https://doi.org/10.1038/nrm3947
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DOI: https://doi.org/10.1038/nrm3947
