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.

细胞衰老或增殖潜能的终末丧失， 有充分的证据表明，在连续传代培养的正常人细胞中， 体外 细胞融合研究表明， 衰老比永生占主导地位， 融合，涉及永生的人类细胞，已经定义了四个 不确定分裂的互补群。 微细胞融合 方法已经确定了细胞衰老相关基因的存在， 在第4、1和7号染色体上分别为B、C和D群。 更 最近，使用抗死亡蛋白的抗体， 已经发现了区分正常细胞和永生细胞的模式， 以及确定永生细胞与之互补的互补群 分配。 有趣的是，死亡蛋白的模式恢复到正常的模式， 微细胞杂交体中的细胞，在以下情况下表现出增殖丧失 将人类1号和7号染色体导入永生细胞 分别分配到C组和D组。 (We尚未研究 通过引入人类4号染色体获得的微细胞杂交体 分配到B组的永生细胞中）。 这项建议的目的是 因此，为了确定在特定亚细胞中的定位是否 隔室负责这种染色差异，并且 导致观察到的差异染色的分子机制。 结果将增加我们对参与的机制的理解， 细胞衰老和永生化。