Fecha de publicación: -- Fuente: PubMed "nature biotechnology" Acta Biochim Biophys Sin (Shanghai). 2026 Nov 9. doi: 10.3724/abbs.2026167. Online ahead of print.ABSTRACTCuproptosis is a recently coined term that refers to a distinct form of cell death driven primarily by copper accumulation. However, the role of the transcription factor Yin Yang 1 (YY1) in copper homeostasis and cuproptosis remains poorly understood. In this study, we demonstrate that YY1 expression is elevated in patients with glioblastoma (GBM) and correlates with both copper homeostasis and cuproptosis. YY1 depletion significantly increases the sensitivity of glioma cells to cuproptosis, whereas YY1 overexpression inhibits this type of cell death. YY1 plays a critical role in cuproptosis by modulating intracellular glutathione (GSH) levels and dihydrolipoamide S-acetyltransferase (DLAT) oligomerization in response to copper ionophores. Mechanistically, YY1 prevents cuproptosis by regulating the expression of aldehyde dehydrogenase 1 family member A3 ( ALDH1A3) and metallothionein ( MT) genes through its interactions with specificity protein 1 (Sp1) and metal regulatory transcription factor 1 (MTF1), respectively. Silencing YY1 in an orthotopic glioblastoma mouse model, combined with disulfiram/copper (DSF/Cu) treatment, inhibited GBM progression and prolonged mouse survival. In summary, these findings reveal a novel mechanism by which YY1 suppresses cuproptosis through interactions with Sp1 and MTF1, suggesting that combined YY1 inhibition with copper ionophore treatment represents a promising therapeutic strategy for GBM.PMID:43002217 | DOI:10.3724/abbs.2026167