Park_2015_BMB.Rep_48_301

Reference

Title : NDRG3-mediated lactate signaling in hypoxia - Park_2015_BMB.Rep_48_301
Author(s) : Park KC , Lee DC , Yeom YI
Ref : BMB Rep , 48 :301 , 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.

PubMedSearch : Park_2015_BMB.Rep_48_301
PubMedID: 25936780

Related information

Citations formats

Park KC, Lee DC, Yeom YI (2015)
NDRG3-mediated lactate signaling in hypoxia
BMB Rep 48 :301

Park KC, Lee DC, Yeom YI (2015)
BMB Rep 48 :301