MORTALIN GENE IN NORMAL AND IMMORTAL HUMAN CELLS

正常和永生人类细胞中的 Mortalin 基因

• 批准号: 6299366
• 负责人: OLIVIA M. PEREIRA-SMITH
• 金额: $ 21.16万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299366
• 关键词: cell fusion; cell line; cell senescence; cell transformation; gene expression; histology; human genetic material tag; hybrid cells; immunologic assay /test; intracellular transport; stainings; tissue /cell culture

Cellular senescence, or terminal loss of proliferative potential, has been well documented to occur in normal human cells serially subcultured in vitro. Cell fusion studies have demonstrated that the phenotype of senescence is dominant over that of immortality, and additional cell fusions, involving immortal human cells, have defined four complementation groups for indefinite division. Microcell fusion approaches have identified the presence of cell senescence genes related to groups B, C and D, on chromosomes 4, 1 and 7, respectively. More recently, using antibodies against the protein mortalin, immunostaining patterns have been found to distinguish normal from immortal cells, as well as identify the complementation group to which the immortal cell assigns. Interestingly, the mortalin pattern returns to that of a normal cell in microcell hybrids that exhibit loss of proliferation following the introduction of human chromosomes 1 and 7, into immortal cells assigned to groups C and D, respectively. (We have not yet studied microcell hybrids obtained from the introduction of human chromosome 4 into immortal cells assigned to group B). The aims of this proposal are therefore to determine whether localization in a particular subcellular compartment is responsible for this difference in staining, and the molecular mechanisms that result in the differential staining observed. The results will increase our understanding of the mechanisms involved in cellular senescence and immortalization.

细胞衰老或终末丧失增殖潜力，具有 有充分的文献记录在正常的人类细胞串行下培养中 体外。 细胞融合研究表明 衰老在不朽和其他细胞上是主导的 涉及不朽人类细胞的融合已定义了四个 无限期分裂的互补组。 Microcell融合 方法已经确定了细胞衰老基因相关的存在 分别在染色体4、1和7上进行B组，C和D组。 更多的 最近，使用针对蛋白质lort蛋白的抗体，免疫染色 已经发现模式将正常与不朽细胞区分开 以及确定不朽细胞的互补组 分配。 有趣的是，Mortalin模式返回到正常 微孔杂种中表现出增殖损失之后的细胞 人类染色体1和7引入不朽细胞 分别分配给C组和D组。 （我们尚未研究 从引入人类染色体4的Microcell杂种 进入分配给B组的不朽细胞。 该提议的目的是 因此，确定是否在特定亚细胞中定位 隔间对这种染色的差异负责， 观察到差异染色的分子机制。 结果将增加我们对涉及机制的理解 细胞衰老和永生化。