期刊
MOLECULAR & CELLULAR ONCOLOGY
卷 6, 期 5, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/23723556.2019.1618174
关键词
Neddylation; EGFR; AKT1; tumor-sphere; ciliogenesis; PKM2; glycolysis; dimerization; tetramerization
类别
资金
- Natural Science Foundation of Zhejiang Province [LY17C070001]
- National Natural Science Foundation of China [81572718]
- Chinese NSFC [31701167]
- National Key R&D Program of China [2016YFA0501800]
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.
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