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NDRG3-mediated lactate signaling in hypoxia
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  • Journal title : BMB Reports
  • Volume 48, Issue 6,  2015, pp.301-302
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.6.080
 Title & Authors
NDRG3-mediated lactate signaling in hypoxia
Park, Kyung Chan; Lee, Dong Chul; Yeom, Young Il;
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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]
Hypoxia;Lactate signaling;NDRG3;HIF-independent hypoxia responses;PHD2/VHL pathway;
 Cited by
Hypoxic repression of CYP7A1 through a HIF-1α- and SHP-independent mechanism, BMB Reports, 2016, 49, 3, 173  crossref(new windwow)