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Human HDAC6 senses valine abundancy to regulate DNA damage 期刊论文

编号：

793A026F9F0321F38930D0CE995AD7DB
作者：

Jin, Jiali#^[1]Meng, Tong#^[1,2]Yu, Yuanyuan#^[3]Wu, Shuheng#^[4]Jiao, ChenChen^[1];Song, Sihui^[1];Li, YaXu^[1];Zhang, Yu^[1];Zhao, YuanYuan^[1];Li, Xinran^[1];Wang, Zixin^[5];Liu, YuFan^[1];Huang, Runzhi^[1];Qin, Jieling^[1];Chen, Yihua(陈益华)^[6,7,8,9]Cao, Hao^[10];Tan, Xiao^[1];Ge, Xin^[1];Jiang, Cong^[1];Xue, Jianhuang^[5];Yuan, Jian^[11];Wu, Dianqing^[12];Wu, Wei^[4];Jiang, CiZhong^[3];Wang, Ping*^[1]
语种：

英文
期刊：

NATURE ISSN：0028-0836 2025 年 637 卷 8044 期 ; JAN 2
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摘要：

As an essential branched amino acid, valine is pivotal for protein synthesis, neurological behaviour, haematopoiesis and leukaemia progression1-3. However, the mechanism by which cellular valine abundancy is sensed for subsequent cellular functions remains undefined. Here we identify that human histone deacetylase 6 (HDAC6) serves as a valine sensor by directly binding valine through a primate-specific SE14 repeat domain. The nucleus and cytoplasm shuttling of human, but not mouse, HDAC6 is tightly controlled by the intracellular levels of valine. Valine deprivation leads to HDAC6 retention in the nucleus and induces DNA damage. Mechanistically, nuclear-localized HDAC6 binds and deacetylates ten-eleven translocation 2 (TET2) to initiate active DNA demethylation, which promotes DNA damage through thymine DNA glycosylase-driven excision. Dietary valine restriction inhibits tumour growth in xenograft and patient-derived xenograft models, and enhances the therapeutic efficacy of PARP inhibitors. Collectively, our study identifies human HDAC6 as a valine sensor that mediates active DNA demethylation and DNA damage in response to valine deprivation, and highlights the potential of dietary valine restriction for cancer treatment. The histone deacetylase HDAC6 is a sensor of valine levels, and the abundance of valine in cells regulates DNA damage and cell homeostasis functions.
推荐引用方式
GB/T 7714：

Jin Jiali,Meng Tong,Yu Yuanyuan, et al. Human HDAC6 senses valine abundancy to regulate DNA damage [J].NATURE,2025,637(8044).
APA：

Jin Jiali,Meng Tong,Yu Yuanyuan,Wu Shuheng,&Wang Ping.(2025).Human HDAC6 senses valine abundancy to regulate DNA damage .NATURE,637(8044).
MLA：

Jin Jiali, et al. "Human HDAC6 senses valine abundancy to regulate DNA damage" .NATURE 637,8044(2025).
入库时间：

2024/12/9 21:36:53
更新时间：

2026/6/1 1:42:36
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