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首页> 外文期刊>Molecular and Cellular Biology >Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis.
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Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis.

机译：p53蛋白的核积累是由几个核定位信号介导的，并在肿瘤发生中起作用。

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The basic carboxy terminus of p53 plays an important role in directing the protein into the nuclear compartment. The C terminus of the p53 molecule contains a cluster of several nuclear localization signals (NLSs) that mediate the migration of the protein into the cell nucleus. NLSI, the most active domain, is highly conserved in genetically diverged species and shares perfect homology with consensus NLS sequences found in other nuclear proteins. The other two NLSs, II and III, appear to be less effective and less conserved. Although nuclear localization is dictated primarily by the NLSs inherent in the primary amino acid sequence, the actual nuclear homing can be modified by interactions with other proteins expressed in the cell. Comparison between wild-type p53 and naturally occurring mutant p53 showed that both protein categories could migrate into the nucleus of rat primary embryonic fibroblasts by essentially similar mechanisms. Nuclear localization of both proteins was totally dependent on the existence of functional NLS domains. In COS cells, however, we found that NLS-deprived wild-type p53 molecules could migrate into the nucleus by complexing with another nuclear protein, simian virus 40 large-T antigen. Wild-type and mutant p53 proteins differentially complexed with viral or cellular proteins, which may significantly affect the ultimate compartmentalization of p53 in the cell; this finding suggests that the actual subcellular compartmentalization of proteins may differ in various cell type milieux and may largely be affected by the ability of these proteins to complex with other proteins expressed in the cell. Experiments designed to test the physiological significance of p53 subcellular localization indicated that nuclear localization of mutant p53 is essential for this protein to enhance the process of malignant transformation of partially transformed cells, suggesting that p53 functions within the cell nucleus.
机译：p53的碱性羧基末端在将蛋白质导入核区室中起着重要作用。 p53分子的C末端包含几个核定位信号（NLSs）的簇，它们介导蛋白质向细胞核的迁移。 NLSI是最活跃的域，在遗传多样性物种中高度保守，并且与其他核蛋白中发现的共有NLS序列具有完美的同源性。其他两个NLS，即II和III，似乎效率较低且保守程度较低。尽管核定位主要由一级氨基酸序列中固有的NLS决定，但实际的核归巢可以通过与细胞中表达的其他蛋白质相互作用来进行修饰。野生型p53和天然存在的突变体p53的比较表明，这两种蛋白都可以通过基本相似的机制迁移到大鼠原代胚胎成纤维细胞的核中。两种蛋白质的核定位完全取决于功能性NLS结构域的存在。然而，在COS细胞中，我们发现被NLS剥夺的野生型p53分子可通过与另一种核蛋白猿猴病毒40大T抗原复合而迁移到细胞核中。野生型和突变型p53蛋白与病毒或细胞蛋白差异复合，可能显着影响p53在细胞中的最终区室化;该发现表明，蛋白质的实际亚细胞区室化在各种细胞类型环境中可能不同，并且可能很大程度上受这些蛋白质与细胞中表达的其他蛋白质复合的能力影响。设计用于测试p53亚细胞定位的生理学意义的实验表明，突变体p53的核定位对于该蛋白增强部分转化细胞的恶性转化过程至关重要，表明p53在细胞核内起作用。

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