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METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and promoting PSMB5 translation - PubMed

3 hours ago
  • #METTL16
  • #multiple myeloma
  • #proteasome inhibitor resistance
  • METTL16 enhances proteasome inhibitor (PI) resistance in multiple myeloma (MM) through a mechanism independent of its m6A methyltransferase activity.
  • Overexpression of METTL16 alters PERK-eIF2α interaction, reduces eIF2α phosphorylation, and increases translation of key transcripts like PSMB5 and CCND1.
  • Increased translation of PSMB5 and CCND1 leads to higher proteasome activity and proliferative capacity in MM cells.
  • Pharmacological targeting of METTL16 improves the efficacy of multiple PIs in MM cells.
  • The study suggests METTL16 as a potential therapeutic target to enhance PI-based therapy in MM.