Inhibition of USP7 destabilizes the noncanonical PRC1.1 complex and induces neuroblastoma differentiation - PubMed
5 hours ago
- #PRC1.1 complex
- #USP7 inhibition
- #neuroblastoma
- Inhibition of USP7 destabilizes the noncanonical PRC1.1 complex and induces neuroblastoma differentiation.
- The non-canonical PRC1.1 complex is identified as a selectively enriched dependency in neuroblastoma, repressing transcriptional activity through H2AK119Ub.
- Knockout of PRC1.1 subunits reduces neuroblastoma growth by inducing neuronal differentiation.
- USP7 inhibition (via XL177A) significantly reduces neuroblastoma growth in cellular and animal models.
- USP7 inhibition disrupts PRC1.1 complex assembly, leading to its destabilization and proteolysis.
- Findings suggest therapeutic potential for USP7 inhibitors in neuroblastoma treatment by targeting epigenetic repression of differentiation programs.