Paper Citing NAMD - Abstract
Gu, Ying; Zhou, Hong; Gan, Yichao; Zhang, Jiawei; Chen, Jianghua; Gan, Xiaoxian; Li, Hongzhi; Zheng, Weiwei; Meng, Zhipeng; Ma, Xiaoxiao; Wang, Xichun; Xu, Xiaohua; Xu, Ganyu; Lu, Xiaoya; Liang, Yun; Zhang, Xuzhao; Lu, Xinliang; Huang, Wendong; Xu, Rongzhen
Small-molecule induction of phospho-eIF4E sumoylation and degradation via targeting its phosphorylated serine 209 residue
ONCOTARGET, 6:15111-15121, JUN 20 2015
As phospho-eIF4E (p-eIF4E), unlike total eIF4E (t-eIF4E) essential for normal cells, is specifically required by cancer cells, it is an attractive, yet unrealized, target for anti-tumor intervention. Here we identify a small molecule, homoharringtonine (HHT), that antagonizes p-eIF4E function and eradicates acute myeloid leukemia (AML) expressing high level of p-eIF4E in vitro and in vivo. HHT selectively reduces p-eIF4E levels of leukemia cells without affecting t-eIF4E. HHT targets the phosphorylated serine 209 residue of p-eIF4E and induces p-eIF4E oligomerization, which enhances its interaction with the small ubiquitin-like protein modifier (SUMO)conjugating enzyme UBC9, resulting in proteasome-dependent degradation of p-eIF4E via SUMO2/3-mediated SUMOylation. These results suggest that the phosphorylated serine 209 residue of p-eIF4E might be a potential target for developing small molecule-based new therapies for leukemia.
