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学科主题: 基础医学
题名:
Cellular uptake of exogenous human PDCD5 protein
作者: Wang, Ying; Li, Dan; Fan, Hui; Tian, Linjie; Zhong, Yingcheng; Zhang, Yingmei; Yuan, Lan; Jin, Caining; Yin, Caihua; Ma, Dalong
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2006-08-25
DOI: 10.1074/jbc.M600183200
卷: 281, 期:34, 页:24803-24817
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: HUMAN-IMMUNODEFICIENCY-VIRUS ; HEPARAN-SULFATE PROTEOGLYCANS ; GENE-EXPRESSION PROFILES ; GPI-ANCHORED PROTEINS ; TAT-FUSION PROTEINS ; MEMBRANE DOMAINS ; LIPID RAFTS ; ACTIN CYTOSKELETON ; GROWTH-FACTOR ; TRANSDUCTION DOMAINS
英文摘要:

PDCD5 (human programmed cell death 5) plays a significant role in apoptotic and paraptotic cell deaths. However, it was found that recombinant PDCD5 added exogenously to culture medium could also enhance programmed cell death triggered by certain stimuli. Here we show that PDCD 5 has a remarkable role in intercellular transport in various cells (endogenous caveolin-1-positive and - negative cells) through a clathrin-independent endocytic pathway that originates from heparan sulfate proteoglycan binding and lipid rafts. These conclusions are supported by the studies of slow internalization kinetics of PDCD5 endosomes, by the resistance of endosomes to nonionic detergents, by the overexpression of the clathrin dominant negative mutant form, which did not block PDCD5-fluorescein isothiocyanate uptake, and by PDCD5 localization in lipid rafts by immunofluorescence, electron microscopy techniques, and sucrose density centrifugation. This is further supported by the findings that certain drugs that disrupt lipid rafts, compete with cell membrane heparan sulfate proteoglycans, or block the caveolae pathway, impair the PDCD5 internalization process. The translocation activity of PDCD5 may possess physiological significance and be a potential mechanism for its programmed cell death-promoting activity. PDCD5 protein also has the ability to drive the internalization of large protein cargo, depending on the residues 109 - 115 mapped by deletion mutagenesis, and can introduce the Mdm-2 binding domain of human p53 into living cells to induce cell death in human cancer cells, indicating that PDCD5 may serve as a vehicle and thus have potential in the field of protein delivery to the cells. This is the first evidence of such findings.

语种: 英语
WOS记录号: WOS:000239847800076
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55853
Appears in Collections:基础医学院_北京大学人类疾病基因研究中心_期刊论文

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作者单位: 1.Peking Univ, Ctr Human Dis Genom, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Med Immunol, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Peking Univ Med & Hlth Anal Ctr, Beijing 100083, Peoples R China

Recommended Citation:
Wang, Ying,Li, Dan,Fan, Hui,et al. Cellular uptake of exogenous human PDCD5 protein[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2006,281(34):24803-24817.
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