The KDM6 histone H3K27me3 demethylase inhibitor GSK-J4 induces metal and stress responses in multiple myeloma cells.

ABSTRACT: Thioneins are cysteine-rich apoproteins that regulate divalent metal homeostasis by virtue of their metal-chelation properties resulting in the ligand-bound metallothionein state. Previous studies show transient upregulation of the metallothionein (MT) gene cluster as part of a complex transcriptional response to a class of histone H3K27me3 demethylase tool compounds targeting human Fe²⁺ dependent ketoglutarate oxygenases KDM6A (UTX) and KDM6B (JmjD3). The prototypic bioactive KDM6 inhibitor GSK-J4 induces apoptotic cell death in multiple myeloma cells and corresponding transcriptomic profiles are dominated by metal and integrated stress response (ISR) signatures, also observed in primary human myeloma cells. Here we investigate the hypothesis that metal-chelation by GSK-J4 prov

SUBMITTER: Cribbs AP 

PROVIDER: S-EPMC13470865 | biostudies-literature | 2026 Oct

REPOSITORIES: biostudies-literature