KDM6A phosphorylation suppresses PER2 to confer a glycolytic vulnerability in HNSCC.

ABSTRACT:

Abstact

As a key tumor suppressor, KDM6A plays critical roles in maintaining epigenetic homeostasis and suppressing tumorigenesis. However, the regulatory mechanisms controlling KDM6A activity in head and neck squamous cell carcinoma (HNSCC) are not well defined. In this study, we employed tissue microarray analysis of clinical specimens to identify Ser829 as a predominant phosphorylation site of KDM6A in HNSCC and other solid tumors. Using mass spectrometry and biochemical assays, we demonstrate that CDK1-mediated phosphorylation at Ser829 enhances KDM6A binding to SFN, leading to its nuclear export and functional inactivation. Integrated chromatin profiling and metabolic analyses revealed that phosphorylated KDM6A-pSer829 drives glycolytic reprogramming through H3K27Me3-dependent

SUBMITTER: Chen J 

PROVIDER: S-EPMC12583727 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature