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NDRG3-mediated lactate signaling in hypoxia
NDRG3-mediated lactate signaling in hypoxia
BMB Reports. 2015. Jun, 48(6): 301-302
Copyright © 2015, Korean Society for Biochemistry and Molecular Biology
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Received : April 27, 2015
  • Published : June 30, 2015
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About the Authors
Kyung Chan Park
Genome Structure Research Center
Dong Chul Lee
Genome Structure Research Center
Young Il Yeom
Ochang Branch Institute, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-806, Korea
yeomyi@kribb.re.kr

Abstract
Hypoxia is associated with many pathological conditions as well as the normal physiology of metazoans. We identified a lactate-dependent signaling pathway in hypoxia, mediated by the oxygen- and lactate-regulated protein NDRG family member 3 (NDRG3). Oxygen negatively regulates NDRG3 expression at the protein level via the PHD2/VHL system, whereas lactate, produced in excess under prolonged hypoxia, blocks its proteasomal degradation by binding to NDRG3. We also found that the stabilized NDRG3 protein promotes angiogenesis and cell growth under hypoxia by activating the Raf-ERK pathway. Inhibiting cellular lactate production abolishes NDRG3-mediated hypoxia responses. The NDRG3-Raf-ERK axis therefore provides the genetic basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases in addition to advancing our understanding of the normal physiology of hypoxia responses. [BMB Reports 2015; 48(6): 301-302]
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Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2010-0030020, NRF-2011-0028171, NRF-2013M3A9B5076422) and by the KRIBB Research Initiative Program.
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