MLN4924: additional activities beyond neddylation inhibition

Abstract

MLN4924, a small molecular inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8) activating enzyme (NAE), blocks cullin neddylation to inactivate cullin-RING ligase. We found that MLN4924 has additional activities: it triggers EGFR dimerization and activation of RAS/MAPK and PI3K/AKT1 signals to stimulate tumor sphere formation and inhibit ciliogenesis; and it triggers PKM2 tetramerization to promote glycolysis.

Keywords

• neddylation
• egfr
• akt1
• tumor-sphere
• ciliogenesis
• pkm2
• glycolysis
• dimerization
• tetramerization