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BNIP3 is degraded by ULK1-dependent autophagy via MTORC1 and AMPK
- BNIP3 is degraded by ULK1-dependent autophagy via MTORC1 and AMPK
- Park, Chang Wook; Hong, Sun Mi; Kim, Eung-Sam; Kwon, Jung Hee; Kim, Kyong-Tai; Nam, Hong Gil; Choi, Kwan Yong
- DGIST Authors
- Nam, Hong Gil
- Issue Date
- Autophagy, 9(3), 345-360
- Article Type
- AMPK; Autophagy; BECN1; BNIP3; Controlled Study; Down-Regulation; Enzyme Regulation; Female; Genetic Transcription; Human; Human Cell; Hydroxymethylglutaryl Coenzyme A Reductase Kinase; Hypoxia; Hypoxia-Inducible Factor-1 Alpha; Kwashiorkor; Macroautophagy; Mammalian Target of Rapamycin Complex 1; Microtubule Associated Protein 1; Mitochondrion; MTOR; Phosphotransferase; Proteasome; Protein BNip3; Protein Degradation; Signal Transduction; Starvation; Torin1; ULK1; UNC 51 Like Kinase; Unclassified Drug
- BNIP3 (BCL2/adenovirus E1B 19 kDa interacting protein 3) is an atypical BH3-only protein that is induced by hypoxiainducible factor 1 (HI F1) under hypoxia. BNIP3 is primarily regulated at the transcriptional level. However, little is known about the underlying mechanism of BNIP3 degradation. In this study, we found that BNIP3 was downregulated when hypoxia was accompanied by amino acid starvation. The BNIP3 downregulation did not occur at the transcription level and was independent of HI F1A. BNIP3 was primarily degraded by the proteasome, but BNIP3 was subjected to both proteasomal and autophagic degradation in response to starvation. The autophagic degradation of BNIP3 was dependent on ATG7 and MAP1LC3. We determined that autophagic degradation of BNIP3 was specifically regulated by ULK1 via the MTOR-AMPK pathway. Moreover, we confirmed that BNIP3 could play a protective role in tumor cells under hypoxia, and the treatment with Torin1, an MTOR inhibitor, decreased the BNIP3 level and enhanced the death of hypoxic tumor cells. © 2013 Landes Bioscience.
- Taylor and Francis Inc.
- Related Researcher
Nam, Hong Gil
CBRG(Complex Biology Research Group)
Plant Aging and Life History; Systems Biology; Complexbiology; Comparative Aging Research
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- Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles
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