Histone Demethylase UTX Suppresses Tumor Cell Proliferation by Regulating Stress Granules.

ABSTRACT: UTX (also known as KDM6A) is a histone H3K27 demethylase that acts as an important tumor regulator. UTX has been reported to participate in genome-wide histone modifications and gene expression in tumorigenesis and its mutations are identified in human cancers. Here, UTX is demonstrated to localize both in the cytoplasm and nucleus, notably, cytoplasmic UTX forms puncta and co-localizes in stress granules (SGs) upon different stresses in vitro. Mechanistically, the TPR domain of UTX plays a critical role in regulating SG disassembly by interacting with G3BP1, the central hub of SG, to disrupt the scaffold network of SG under endoplasmic reticulum stress. Importantly, a clinical UTX mutation, D336G in TPR domain, increases cytoplasmic location of UTX, and stabilizes SG. While UTX^D336G<

SUBMITTER: Liu X 

PROVIDER: S-EPMC12442641 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature