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NDRG3-mediated lactate signaling in hypoxia
#MMPMID25936780
Park KC
; Lee DC
; Yeom YI
BMB Rep
2015[Jun]; 48
(6
): 301-2
PMID25936780
show ga
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.
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