NDRG3-mediated lactate signaling in hypoxia.

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.

journal_name

BMB Rep

journal_title

BMB reports

authors

Park KC,Lee DC,Yeom YI

doi

10.5483/bmbrep.2015.48.6.080

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

301-2

issue

6

eissn

1976-6696

issn

1976-670X

pii

3215

journal_volume

48

pub_type

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