期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 292, 期 39, 页码 16211-16220出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.769950
关键词
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资金
- National Institutes of Health [RO1 CA39481, RO1 CA47282, RO1 CA164462, 5T32 AR060715-05]
- Biotechnology and Biological Sciences Research Council [1618838] Funding Source: researchfish
- NATIONAL CANCER INSTITUTE [R01CA164462, R01CA047282, R01CA039481] Funding Source: NIH RePORTER
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.
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