NUDIX5 通过 ADP-核糖衍生的核 ATP 合成对于染色质重塑是必需的。

ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling.

机构信息

Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.

Universitat Pompeu Fabra, Barcelona E-08003, Spain. Structural Bioinformatics Laboratory, Universitat Pompeu Fabra, Barcelona E-08003, Spain.

出版信息

Science. 2016 Jun 3;352(6290):1221-5. doi: 10.1126/science.aad9335.

DOI:10.1126/science.aad9335

PMID:27257257

Abstract

Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation.

摘要

真核生物中的关键核过程，包括 DNA 复制、修复和基因调控，都需要由消耗能量的酶来催化广泛的染色质重塑。目前尚不清楚这些过程的 ATP 需求如何在快速刺激下得到满足。我们在孕激素诱导的乳腺癌细胞中大规模基因调控变化的背景下分析了这个问题，发现细胞内通过多聚（ADP-核糖）水解生成 ADP-核糖来产生 ATP。在焦磷酸的存在下，焦磷酸酶 NUDIX5 利用 ADP-核糖生成核 ATP。核 ATP 的产生对于激素诱导的染色质重塑、转录调控和细胞增殖是必不可少的。