Document Type
Article
Publication Date
9-29-2017
Abstract
Macroautophagy is a fundamental and evolutionarily conserved catabolic process that eradicates damaged and aging macromolecules and organelles in eukaryotic cells. Decorin, an archetypical small leucine-rich proteoglycan, initiates a protracted autophagic program downstream of VEGF receptor 2 (VEGFR2) signaling that requires paternally expressed gene 3 (PEG3). We have discovered that PEG3 is an upstream transcriptional regulator of transcription factor EB (TFEB), a master transcription factor of lysosomal biogenesis, for decorin-evoked endothelial cell autophagy. We found a functional requirement of PEG3 for TFEB transcriptional induction and nuclear translocation in human umbilical vein endothelial and PAER2 cells. Mechanistically, inhibiting VEGFR2 or AMP-activated protein kinase (AMPK), a major decorin-activated energy sensor kinase, prevented decorin-evoked TFEB induction and nuclear localization. In conclusion, our findings indicate a non-canonical (nutrient- and energy-independent) mechanism underlying the pro-autophagic bioactivity of decorin via PEG3 and TFEB.
Recommended Citation
Neill, Thomas; Sharpe, Catherine; Owens, Rick T.; and Iozzo, Renato V., "Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy." (2017). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 221.
https://jdc.jefferson.edu/pacbfp/221
PubMed ID
28798237
Comments
This research was originally published in Journal of Biological Chemistry. Neill, T., Sharpe, C., Owens, R. T., & Iozzo, R. V.. Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy. Journal of Biological Chemistry. 2017; 292(39):16211-16220. © the American Society for Biochemistry and Molecular Biology.