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Peptide degrader-based targeting of METTL3/14 improves immunotherapy response in cutaneous melanoma

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2024-08; 
Hong Han , Zenghui Li , Yuqing Feng , He Song , Zhixiong Fang , Dingxiao Zhang , Dan Yuan , Junfeng Shi
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Recombinant Proteins SK-MEL-28 cells (0.1 × 104/well) were seeded into 24-well ultra-low attachment plates (Corning Costar) in serumfree DMEM/F12 (HyClone) supplemented with human 10 ng/mL EGF (Z00333, GenScript Biotech Corporation), 20 ng/mL bFGF (HY-P7330, MedChemExpress, Monmouth Junction, NJ, USA), and 1% (v/v) B27 (15444-H01H, Sino Biological Inc. China). Get A Quote

摘要

METTL3 has emerged as a promising therapeutic target in cancer treatment, although its oncogenic functions in melanoma development and potential for therapeutic targeting drug have not been fully explored. In this study, we define the oncogenic role of METTL3 in melanoma development and progression. Building on this insight, we examine our recently designed peptide inhibitor RM3, which targets the binding interface of METTL3/14 complex for disruption and subsequent ubiquitin-mediated proteasomal degradation via the E3 ligase STUB1. RM3 treatment reduces proliferation, migration, and invasion, and induces apoptosis in melanoma cells in vitro and in vivo. Subsequent transcriptomic analysis identified changes in i... More

关键词

Degradation; Immunotherapy; METTL3; Melanoma; peptide.