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送上死亡之吻:对穿孔素作用机制的理解进展

Delivering the kiss of death: progress on understanding how perforin works.

作者信息

Pipkin Matthew E, Lieberman Judy

机构信息

CBR Institute for Biomedical Research, Harvard Medical School, Boston MA 02115, USA.

出版信息

Curr Opin Immunol. 2007 Jun;19(3):301-8. doi: 10.1016/j.coi.2007.04.011. Epub 2007 Apr 12.

DOI:10.1016/j.coi.2007.04.011
PMID:17433871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11484871/
Abstract

Killer lymphocytes release perforin and granzymes from cytotoxic granules into the immunological synapse to destroy target cells as a critical mechanism in the defense against viruses and cancer. Perforin, a Ca(2+)-dependent pore-forming protein that multimerizes in membranes, delivers granzymes into the target cell cytosol. The original model for perforin (acting by forming a cell membrane channel through which granzymes pass) does not fit the experimental data. Recently, an alternative model has been proposed that involves active target cell collaboration with perforin to deliver granzymes and direct the target cell to an apoptotic, rather than necrotic, death.

摘要

杀伤性淋巴细胞将穿孔素和颗粒酶从细胞毒性颗粒释放到免疫突触中,以破坏靶细胞,这是抵御病毒和癌症的关键机制。穿孔素是一种依赖钙离子的成孔蛋白,可在膜中形成多聚体,将颗粒酶递送至靶细胞胞质溶胶中。最初的穿孔素模型(通过形成供颗粒酶通过的细胞膜通道起作用)并不符合实验数据。最近,有人提出了一种替代模型,该模型涉及靶细胞与穿孔素的主动协作,以递送颗粒酶并将靶细胞导向凋亡而非坏死性死亡。

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本文引用的文献

1
Granzyme K directly processes bid to release cytochrome c and endonuclease G leading to mitochondria-dependent cell death.颗粒酶K直接切割Bid以释放细胞色素c和核酸内切酶G,从而导致线粒体依赖性细胞死亡。
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Chromosome transfer activates and delineates a locus control region for perforin.染色体转移激活并界定了穿孔素的一个基因座控制区。
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Perforin-mediated target-cell death and immune homeostasis.穿孔素介导的靶细胞死亡与免疫稳态。
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4
Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of target cells.颗粒酶K切割核小体组装蛋白SET以诱导靶细胞的单链DNA切口。
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Cytotoxic T lymphocytes from cathepsin B-deficient mice survive normally in vitro and in vivo after encountering and killing target cells.来自组织蛋白酶B缺陷小鼠的细胞毒性T淋巴细胞在遇到并杀死靶细胞后,在体外和体内均可正常存活。
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Granzyme M directly cleaves inhibitor of caspase-activated DNase (CAD) to unleash CAD leading to DNA fragmentation.颗粒酶M直接切割半胱天冬酶激活的脱氧核糖核酸酶(CAD)抑制剂,释放CAD,导致DNA片段化。
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Granule-mediated killing by granzyme B and perforin requires a mannose 6-phosphate receptor and is augmented by cell surface heparan sulfate.颗粒酶B和穿孔素介导的颗粒杀伤作用需要一种6-磷酸甘露糖受体,并且细胞表面硫酸乙酰肝素可增强这种作用。
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Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis.穿孔素触发质膜修复反应,促进细胞毒性T淋巴细胞诱导的细胞凋亡。
Immunity. 2005 Sep;23(3):249-62. doi: 10.1016/j.immuni.2005.08.001.
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Cationic sites on granzyme B contribute to cytotoxicity by promoting its uptake into target cells.颗粒酶B上的阳离子位点通过促进其被靶细胞摄取而有助于细胞毒性。
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