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Title 

NDRG3-mediated lactate signaling in hypoxia

Authors 

Kyung Chan ParkDong Chul LeeYoung Il Yeom

Publisher 

Korean Society for Biochemistry and Molecular Biology

Issue Date 

2015

Citation 

BMB Reports, vol. 48, no. 6, pp. 301-302

Keywords 

HIF-independent hypoxia responsesHypoxiaLactate signalingNDRG3PHD2/VHL pathway

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.

ISSN 

1976-6696

Link 

http://dx.doi.org/10.5483/BMBRep.2015.48.6.080

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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