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A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking
Alternative TitleA Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking
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)
2008
Source PublicationJ. Biol. Chem.
ISSN0021-9258
Volume283Issue:45Pages:31087-31096
AbstractAn 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.
Subject Area生命有机化学
Department上海有机所; Broad Institute of Harvard and MIT; 哈佛医学院
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Indexed BySCI
Language英语
WOS IDWOS:000260544800063
Citation statistics
Cited Times:31[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/15565
Collection生命有机化学国家重点实验室
Corresponding AuthorMa DW(马大为); Yuan JY(袁钧英)
Recommended Citation
GB/T 7714
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.
APA 潘鹤龄.,俞佳.,张立红.,Carpenter, Anne.,Zhu, Hong.,...&袁钧英.(2008).A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking.J. Biol. Chem.,283(45),31087-31096.
MLA 潘鹤龄,et al."A Novel Small Molecule Regulator of Guanine Nucleotide Exchange Activity of the ADP-ribosylation Factor and Golgi Membrane Trafficking".J. Biol. Chem. 283.45(2008):31087-31096.
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