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学科主题: 生命有机化学
题名: A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking
其他题名: A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking
作者: Pan HL(潘鹤龄) ; Yu J(俞佳) ; Zhang LH(张立红) ; Carpenter, Anne ; Zhu, Hong ; Li L(李莉) ; Ma DW(马大为) ; Yuan JY(袁钧英)
通讯作者: 马大为 ; 袁钧英
刊名: J. Biol. Chem.
发表日期: 2008
卷: 283, 期:45, 页:31087-31096
收录类别: SCI
部门归属: 上海有机所; Broad Institute of Harvard and MIT; 哈佛医学院
英文摘要: An image-based phenotypic screen was developed to identify small molecule regulators of intracellular traffic. Using this screen we found that AG1478, a previously known inhibitor of epidermal growth factor receptor, had epidermal growth factor receptor-independent activity in inducing the disassembly of the Golgi in human cells. Similar to brefeldin A (BFA), a known disrupter of the Golgi, AG1478 inhibits the activity of small GTPase ADP-ribosylation factor. Unlike BFA, AG1478 exhibits low cytotoxicity and selectively targets the cis-Golgi without affecting endosomal compartment. We show that AG1478 inhibits GBF1, a large nucleotide exchange factor for the ADP-ribosylation factor, in a Sec7 domain-dependent manner and mimics the phenotype of a GBF1 mutant that has an inactive mutation. The treatment with AG1478 leads to the recruitment of GBF1 to the vesicular-tubular clusters adjacent to the endoplasmic reticulum exit sites, a step only transiently observed previously in the presence of BFA. We propose that the treatment with AG1478 delineates a membrane trafficking intermediate step that depends upon the Sec7 domain.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000260544800063
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/15565
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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Recommended Citation:
Pan HL,Yu J,Zhang LH,et al. A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking[J]. J. Biol. Chem.,2008,283(45):31087-31096.
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