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The prion protein interacts with Bcl-2 and Bax proteins.

机译:ion病毒蛋白与Bcl-2和Bax蛋白相互作用。

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摘要

The function of the normal cellular human prion protein (PrPC), a highly expressed protein of the brain, is presently unclear. Based on the amino acid sequence homology between PrPC, Bcl-2, and Bax proteins, we propose that PrPC may be implicated in modulating neuronal survival and death as a member of the Bcl-2 family of proteins. The present study investigates interactions between human PrPC, Bcl-2, and Bax in human primary foetal neurons as well as in, human foetal and adult brains by crosslinking and co-immunoprecipitation. The PrPC-Bcl-2 interaction was also tested by the yeast-two-hybrid system. Results indicate an interaction between PrPC and Bcl-2 as well as PrPC and Bax in vivo and in vitro. In addition, the expression levels of PrPC, Bcl-2, and Bax were studied in the cerebellum of human foetal and adult brain. Results show that the levels of Bcl-2 and Bax decrease with age whereas the levels of PrPC increase. In the aging central nervous system, PrPC may functionally replace Bcl-2 or Bax. Overexpression or different modifications of PrPC such as conformational change and mutations may disrupt the protein-protein interactions between PrPC, Bcl-2, and Bax. If PrPC-Bcl-2/Bax interactions function in neuronal survival, disruption of these interactions could explain the underlying molecular mechanism of neuronal death in prion diseases. (Abstract shortened by UMI.)
机译:目前尚不清楚正常细胞人病毒蛋白(PrPC)的功能,后者是大脑中一种高度表达的蛋白。基于PrPC,Bcl-2和Bax蛋白之间的氨基酸序列同源性,我们建议PrPC作为Bcl-2家族蛋白的成员可能参与调节神经元的存活和死亡。本研究通过交联和共免疫沉淀研究人类原代胎儿神经元以及人类胎儿和成年大脑中人类PrPC,Bcl-2和Bax之间的相互作用。 PrPC-Bcl-2相互作用也通过酵母-双杂交系统进行了测试。结果表明,在体内和体外,PrPC和Bcl-2之间以及PrPC和Bax之间存在相互作用。另外,研究了在人胎儿和成年大脑的小脑中PrPC,Bcl-2和Bax的表达水平。结果表明,随着年龄的增长,Bcl-2和Bax的含量下降,而PrPC的含量则升高。在老化的中枢神经系统中,PrPC可能在功能上替代Bcl-2或Bax。 PrPC的过表达或不同修饰(例如构象变化和突变)可能会破坏PrPC,Bcl-2和Bax之间的蛋白质-蛋白质相互作用。如果PrPC-Bcl-2 / Bax相互作用在神经元存活中起作用,则这些相互作用的破坏可以解释病毒疾病中神经元死亡的潜在分子机制。 (摘要由UMI缩短。)

著录项

  • 作者

    Papadopoulos, Maria.;

  • 作者单位

    McGill University (Canada).;

  • 授予单位 McGill University (Canada).;
  • 学科 Biology Neuroscience.
  • 学位 M.Sc.
  • 年度 1998
  • 页码 112 p.
  • 总页数 112
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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