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本文引用的文献

1
Activation of a cysteine protease in MCF-7 and T47D breast cancer cells during beta-lapachone-mediated apoptosis.
Exp Cell Res. 2000 Mar 15;255(2):144-55. doi: 10.1006/excr.1999.4790.
2
NAD(P)H:Quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity.NAD(P)H：醌氧化还原酶活性是β-拉帕醌细胞毒性的主要决定因素。
J Biol Chem. 2000 Feb 25;275(8):5416-24. doi: 10.1074/jbc.275.8.5416.
3
Ku is associated with the telomere in mammals.Ku在哺乳动物中与端粒相关联。
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12454-8. doi: 10.1073/pnas.96.22.12454.
4
Poly(ADP-ribose) polymerase and Ku autoantigen form a complex and synergistically bind to matrix attachment sequences.聚（ADP - 核糖）聚合酶与Ku自身抗原形成复合物，并协同结合至基质附着序列。
J Biol Chem. 1999 Jul 16;274(29):20521-8. doi: 10.1074/jbc.274.29.20521.
5
Oxidative stress inhibits apoptosis in human lymphoma cells.氧化应激抑制人淋巴瘤细胞的凋亡。
J Biol Chem. 1999 Jul 9;274(28):19792-8. doi: 10.1074/jbc.274.28.19792.
6
Ku, a DNA repair protein with multiple cellular functions?Ku，一种具有多种细胞功能的DNA修复蛋白？
Mutat Res. 1999 May 14;434(1):3-15. doi: 10.1016/s0921-8777(99)00006-3.
7
Isolation of Ku70-binding proteins (KUBs).Ku70结合蛋白（KUBs）的分离
Nucleic Acids Res. 1999 May 15;27(10):2165-74. doi: 10.1093/nar/27.10.2165.
8
Molecular analyses of adaptive survival responses (ASRs): role of ASRs in radiotherapy.适应性生存反应（ASRs）的分子分析：ASRs在放射治疗中的作用
Hum Exp Toxicol. 1998 Aug;17(8):448-53. doi: 10.1177/096032719801700809.
9
DNA-dependent protein kinase acts upstream of p53 in response to DNA damage.DNA依赖性蛋白激酶在响应DNA损伤时作用于p53上游。
Nature. 1998 Aug 13;394(6694):700-4. doi: 10.1038/29343.
10
Ku70: a candidate tumor suppressor gene for murine T cell lymphoma.Ku70：一种小鼠T细胞淋巴瘤的候选肿瘤抑制基因。
Mol Cell. 1998 Jul;2(1):1-8. doi: 10.1016/s1097-2765(00)80108-2.

核簇集蛋白/XIP8，一种由X射线诱导产生的与Ku70结合的蛋白，可作为细胞死亡的信号。

Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death.

作者信息

Yang C R, Leskov K, Hosley-Eberlein K, Criswell T, Pink J J, Kinsella T J, Boothman D A

机构信息

Laboratory of Molecular Stress Responses, Departments of Radiation Oncology, Pharmacology and Pathology, Ireland Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue (BRB-326 East), Cleveland, OH 44106-4942, USA.

出版信息

Proc Natl Acad Sci U S A. 2000 May 23;97(11):5907-12. doi: 10.1073/pnas.97.11.5907.

DOI:10.1073/pnas.97.11.5907
PMID:10823943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC18532/
Abstract

Clusterin [CLU, a.k.a. TRPM-2, SGP-2, or ionizing radiation (IR)-induced protein-8 (XIP8)] was implicated in apoptosis, tissue injury, and aging. Its function remains elusive. We reisolated CLU/XIP8 by yeast two-hybrid analyses using as bait the DNA double-strand break repair protein Ku70. We show that a delayed (2-3 days), low-dose (0.02-10 Gy) IR-inducible nuclear CLU/XIP8 protein coimmunoprecipitated and colocalized (by confocal microscopy) in vivo with Ku70/Ku80, a DNA damage sensor and key double-strand break repair protein, in human MCF-7:WS8 breast cancer cells. Overexpression of nuclear CLU/XIP8 or its minimal Ku70 binding domain (120 aa of CLU/XIP8 C terminus) in nonirradiated MCF-7:WS8 cells dramatically reduced cell growth and colony-forming ability concomitant with increased G(1) cell cycle checkpoint arrest and increased cell death. Enhanced expression and accumulation of nuclear CLU/XIP8-Ku70/Ku80 complexes appears to be an important cell death signal after IR exposure.

摘要

聚集素[CLU，又称TRPM - 2、SGP - 2或电离辐射（IR）诱导蛋白8（XIP8）]与细胞凋亡、组织损伤及衰老相关。其功能仍不明确。我们以DNA双链断裂修复蛋白Ku70作为诱饵，通过酵母双杂交分析重新分离出了CLU/XIP8。我们发现，在人MCF - 7:WS8乳腺癌细胞中，一种延迟（2 - 3天）、低剂量（0.02 - 10 Gy）IR诱导的核内CLU/XIP8蛋白在体内与Ku70/Ku80（一种DNA损伤传感器及关键双链断裂修复蛋白）发生共免疫沉淀及共定位（通过共聚焦显微镜观察）。在未受辐射的MCF - 7:WS8细胞中过表达核内CLU/XIP8或其最小的Ku70结合结构域（CLU/XIP8 C末端的120个氨基酸）会显著降低细胞生长及集落形成能力，同时伴有G(1)期细胞周期检查点阻滞增加及细胞死亡增加。核内CLU/XIP8 - Ku70/Ku80复合物的表达及积累增强似乎是IR暴露后一个重要的细胞死亡信号。