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Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2017 Sep 29; Vol. 292 (39), pp. 16211-16220. Date of Electronic Publication: 2017 Aug 10. - Publication Year :
- 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.<br /> (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- AMP-Activated Protein Kinases antagonists & inhibitors
AMP-Activated Protein Kinases metabolism
Active Transport, Cell Nucleus drug effects
Animals
Aorta cytology
Aorta drug effects
Aorta metabolism
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism
Cells, Cultured
Decorin genetics
Endothelium, Vascular cytology
Endothelium, Vascular drug effects
Gene Expression Regulation drug effects
Human Umbilical Vein Endothelial Cells cytology
Human Umbilical Vein Endothelial Cells drug effects
Human Umbilical Vein Endothelial Cells metabolism
Humans
Kruppel-Like Transcription Factors chemistry
Kruppel-Like Transcription Factors genetics
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments metabolism
Protein Kinase Inhibitors pharmacology
RNA Interference
Receptors, Growth Factor metabolism
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins metabolism
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Sus scrofa
Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
Vascular Endothelial Growth Factor Receptor-2 genetics
Vascular Endothelial Growth Factor Receptor-2 metabolism
Autophagy drug effects
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors agonists
Decorin metabolism
Endothelium, Vascular metabolism
Kruppel-Like Transcription Factors metabolism
Receptors, Growth Factor agonists
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 292
- Issue :
- 39
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28798237
- Full Text :
- https://doi.org/10.1074/jbc.M116.769950