Article-summary-12-07-24

Article title

Human HDAC6 senses valine abundancy to regulate DNA damage

HDAC is a sensor of valine leading to DNA damage and potent cancer treatment

Journal

Nature

Tags

Small molecule metabolites; DNA damage; Novel cellular pathways

Introduction

Valine is one of the 20 essential amino acids. Valine takes part in various physiological pathways such as protein synthesis and leukemia genesis. However, how valine is sensed and what downstream effectors recognize valine remain unexplored.

In addition, amino acid sensors mainly sense amino acids to regulate tRNA-related pathway or mTORC related pathway. Whether amino acid sensors regulate pathways except tRNA and mTORC remains unknown.

This work

Here the article discovered that HDAC6, the deacetylase, is a valine sensor. Valine deprivation causes HDAC6 locating at nucleus rather than cytosol. Valine-caused HDAC6 relocation triggered TET2-TDG pathway to induce DNA damage. Moreover, induced valine deprivation could affect tumor growth through HDAC6-TET2-TDG pathway to trigger DNA damage. Low valine level reduced the tumor growth. Thus, valine-triggered HDAC6 sensing might be potential cancer treatment strategy in the future.

doi

10.1038/s41586-024-08248-5