NDRG3-mediated lactate signaling in hypoxia

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Title
NDRG3-mediated lactate signaling in hypoxia
Author(s)
Kyung Chan ParkDong Chul LeeYoung Il Yeom
Bibliographic Citation
BMB Reports, vol. 48, no. 6, pp. 301-302
Publication Year
2015
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.
Keyword
HIF-independent hypoxia responsesHypoxiaLactate signalingNDRG3PHD2/VHL pathway
ISSN
1225-8687
Publisher
South Korea
DOI
http://dx.doi.org/10.5483/BMBRep.2015.48.6.080
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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