Noncanonical role of KDM5C in conferring bortezomib resistance via the PERK‒Nrf2 axis in multiple myeloma - PubMed
3 hours ago
- #KDM5C
- #multiple myeloma
- #bortezomib resistance
- KDM5C has a noncanonical role in conferring bortezomib (BTZ) resistance in multiple myeloma (MM).
- KDM5C binds to CBP and MYC, promoting BTZ resistance via a demethylase-independent mechanism.
- KDM5C is upregulated in BTZ-resistant and relapsed MM patients, inversely correlating with overall survival.
- Depletion of KDM5C increases MM cell sensitivity to BTZ both in vitro and in vivo.
- KDM5C forms a complex with CBP and MYC via its PHD2 domain, triggering H3K27ac enrichment on the PERK promoter.
- This complex activates PERK transcription and promotes Nrf2 phosphorylation, enhancing the unfolded protein response in MM cells.
- KDM5C is a potential therapeutic target for BTZ-resistant MM.