The ADP-ribose reactive NUDIX hydrolase isoforms can modulate HIF-1alpha in cancer cells
- The ADP-ribose reactive NUDIX hydrolase isoforms can modulate HIF-1alpha in cancer cells
- 양은경; 김소연; 윤병분
- ADP-ribose; NUDIX hydrolase; HIF-1alpha; TRPM2; AMPK
- Issue Date
- Biochemical and biophysical research communications
- VOL 504-327
- The human nucleoside-diphosphate linked moiety– X (NUDIX) hydrolases that utilize ADP-ribose and NADH/NAD+ are overexpressed in cancer cells, but their roles in hypoxia inducible factor-1α (HIF-1α) regulation have not yet been revealed. Here, we showed that these NUDIX hydrolases negatively regulated HIF-1α accumulation by modulating the Ca2+ dependent AMP-activated protein kinase (AMPK) signaling pathway. In specific, knockdown of NUDT9 resulted in accumulation of free ADP-ribose that triggered Ca2+ influx mediated by transient receptor potential cation channel subfamily M member 2 and subsequent activation of Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). In addition, AMPK activation by CaMKKβ was shown to enhance HIF-1α accumulation. Our findings provide insights into the action of NUDIX hydrolases as an additional, discrete modulator of HIF-1α accumulation.
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