Arsenic Trioxide Controls the Fate of the PML-RAR alpha Oncoprotein by Directly Binding PML
Zhang, XW; Yan, XJ; Zhou, ZR; Yang, FF; Wu, ZY; Sun, HB; Liang, WX; Song, AX; Lallemand-Breitenbach, V; Jeanne, M; Zhang, QY; Yang, HY; Huang, QH; Zhou, GB; Tong, JH; Zhang, Y; Wu, JH; Hu, HY; de The, H; Chen, SJ; Chen, Z; Yang FF(杨飞飞); Wu ZY(吴自玉)
刊名SCIENCE
2010
卷号328期号:5975页码:#REF!
学科分类Science & Technology - Other Topics
DOI10.1126/science.1183424
通讯作者Chen, SJ (reprint author), Shanghai Jiao Tong Univ, Rui Jin Hosp, Shanghai Inst Hematol, State Key Lab Med Genom,Sch Med, 197 Rui Jin Rd 2, Shanghai 200025, Peoples R China.
文章类型Article
英文摘要Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As(2)O(3)) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RAR alpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RAR alpha degradation is triggered by their SUMOylation, but the mechanism by which As(2)O(3) induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RAR alpha and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)-conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As(2)O(3) provides new insights into the drug's mechanism of action and its specificity for APL.
类目[WOS]Multidisciplinary Sciences
收录类别SCI
WOS记录号WOS:000276459600045
引用统计
被引频次:355[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/227140
专题中国科学院高能物理研究所_多学科研究中心_期刊论文
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Zhang, XW,Yan, XJ,Zhou, ZR,et al. Arsenic Trioxide Controls the Fate of the PML-RAR alpha Oncoprotein by Directly Binding PML[J]. SCIENCE,2010,328(5975):#REF!.
APA Zhang, XW.,Yan, XJ.,Zhou, ZR.,Yang, FF.,Wu, ZY.,...&吴自玉.(2010).Arsenic Trioxide Controls the Fate of the PML-RAR alpha Oncoprotein by Directly Binding PML.SCIENCE,328(5975),#REF!.
MLA Zhang, XW,et al."Arsenic Trioxide Controls the Fate of the PML-RAR alpha Oncoprotein by Directly Binding PML".SCIENCE 328.5975(2010):#REF!.
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