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オバラ チズカ
Obara Chizuka
小原 千寿香 所属 東邦大学 理学部 生物学科 職種 博士研究員 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Nuclear entry mechanism of the human polyomavirus JC virus-like particle: role of importins and the nuclear pore complex. |
| 掲載誌名 | 正式名：The Journal of biological chemistry ISSNコード：0021-9258 |
| 掲載区分 | 国外 |
| 出版社 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 巻・号・頁 | 279(26),pp.27735-42 |
| 著者・共著者 | Qiumin Qu,Hirofumi Sawa,Tadaki Suzuki,Shingo Semba,Chizuka Henmi,Yuki Okada,Masumi Tsuda,Shinya Tanaka,Walter J Atwood,Kazuo Nagashima |
| 発行年月 | 2004/06/25 |
| 概要 | JC virus (JCV) belongs to the polyomavirus family of double-stranded DNA viruses and causes progressive multifocal leukoencephalopathy in humans. Although transport of virions to the nucleus is an important step in JCV infection, the mechanism of this process has remained unclear. The outer shell of the JCV virion comprises the major capsid protein VP1, which possesses a putative nuclear localization signal (NLS), and virus-like particles (VLPs) consisting of recombinant VP1 exhibit a virion-like structure and physiological functions ( cellular attachment and intracytoplasmic trafficking) similar to those of JCV virions. We have now investigated the mechanism of nuclear transport of JCV with the use of VLPs. Wild-type VLPs (wtVLPs) entered the nucleus of most HeLa or SVG cells. The virion structure of VLPs was preserved during transport to the nucleus as revealed by confocal microscopy of cells inoculated with fluorescein isothiocyanate-labeled wtVLPs containing packaged Cy3. The nuclear transport of wtVLPs in digitonin-permeabilized cells was dependent on the addition of importins alpha and beta and was prevented by wheat germ agglutinin or by antibodies to the nuclear pore complex. The nuclear entry of VLPs composed of VP1 with a mutated NLS was greatly inhibited, compared with that of wtVLPs, in both intact and permeabilized cells. Unlike wtVLPs, the mutant VLPs did not bind to importins alpha or beta. Limited proteolysis analysis revealed that the NLS of VP1 was exposed on the surface of wtVLPs. These results suggest that JCV VLPs bind to cellular importins via the NLS of VP1 and are transported into the nucleus through the nuclear pore complex. |
| DOI | 10.1074/jbc.M310827200 |
| PMID | 15069063 |