Yoon, Byungboon Yang, Eun Gyeong Kim, So Yeon 2024-01-19T21:34:47Z 2024-01-19T21:34:47Z 2021-09-04 2018-09-26 0006-291X https://pubs.kist.re.kr/handle/201004/120891 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-1 alpha (HIF-1 alpha) regulation have not yet been revealed. Here, we showed that these NUDIX hydrolases negatively regulated HIF-1 alpha, 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 beta (CaMKK beta). In addition, AMPK activation by CaMKK beta was shown to enhance HIF-1 alpha accumulation. Our findings provide insights into the action of NUDIX hydrolases as an additional, discrete modulator of HIF-1 alpha accumulation. (C) 2018 Published by Elsevier Inc. English ACADEMIC PRESS INC ELSEVIER SCIENCE ACTIVATED PROTEIN-KINASE OXIDATIVE STRESS MESSENGER-RNA CHANNEL TRPM2 OVEREXPRESSION MITOCHONDRIA MECHANISMS GROWTH HIF The ADP-ribose reactive NUDIX hydrolase isoforms can modulate HIF-1 alpha in cancer cells Article 10.1016/j.bbrc.2018.08.185 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.504, no.1, pp.321 - 327 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 504 1 321 327 scie scopus 000446794100049 2-s2.0-85052843565 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article ACTIVATED PROTEIN-KINASE OXIDATIVE STRESS MESSENGER-RNA CHANNEL TRPM2 OVEREXPRESSION MITOCHONDRIA MECHANISMS GROWTH HIF ADP-ribose NUDIX hydrolase HIF-1 alpha TRPM2 AMPK