在沃纳综合征细胞中，p53介导的细胞凋亡减弱。
p53-mediated apoptosis is attenuated in Werner syndrome cells.
作者信息
Spillare E A, Robles A I, Wang X W, Shen J C, Yu C E, Schellenberg G D, Harris C C
机构信息
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
出版信息
Genes Dev. 1999 Jun 1;13(11):1355-60. doi: 10.1101/gad.13.11.1355.
Abstract
The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53- mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients.
摘要
WRN DNA解旋酶是含DExH的DNA解旋酶超家族的成员，该超家族包括XPB、XPD和BLM。在患有早衰和癌症易感性综合征（称为沃纳综合征，WS）的患者中发现了WRN的突变。p53在体内和体外均通过其羧基末端与WRN蛋白结合。WS成纤维细胞的p53介导的凋亡反应减弱，这种缺陷可通过野生型WRN的表达得到挽救。这些数据支持以下假设：p53可通过调节特定的含DExH的DNA解旋酶诱导凋亡，并且可能对WS患者中观察到的癌症易感性具有影响。
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本文引用的文献
1
Werner syndrome protein. I. DNA helicase and dna exonuclease reside on the same polypeptide.维尔纳综合征蛋白。I. DNA解旋酶和DNA外切核酸酶存在于同一条多肽链上。
J Biol Chem. 1998 Dec 18;273(51):34139-44. doi: 10.1074/jbc.273.51.34139.
2
A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity.小鼠沃纳综合征解旋酶内的一个缺失会导致对拓扑异构酶抑制剂敏感，并丧失细胞增殖能力。
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13097-102. doi: 10.1073/pnas.95.22.13097.
3
Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53.Sp1介导的Werner解旋酶基因转录受Rb和p53调控。
Mol Cell Biol. 1998 Nov;18(11):6191-200. doi: 10.1128/MCB.18.11.6191.
4
The premature ageing syndrome protein, WRN, is a 3'-->5' exonuclease.早衰综合征蛋白WRN是一种3'→5'核酸外切酶。
Nat Genet. 1998 Oct;20(2):114-6. doi: 10.1038/2410.
5
Replication focus-forming activity 1 and the Werner syndrome gene product.复制焦点形成活性1与沃纳综合征基因产物。
Nat Genet. 1998 Aug;19(4):375-8. doi: 10.1038/1263.
6
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Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8733-8. doi: 10.1073/pnas.95.15.8733.
7
Nucleolar localization of the Werner syndrome protein in human cells.沃纳综合征蛋白在人细胞中的核仁定位。
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8
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9
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10
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Nat Genet. 1997 Aug;16(4):335-6. doi: 10.1038/ng0897-335.
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