MORTALIN GENE IN NORMAL AND IMMORTAL HUMAN CELLS

细胞衰老，或增殖能力的最终丧失，有 已经有充分的证据表明，在连续传代的正常人类细胞中也会发生这种情况 在试管中。细胞融合研究表明，细胞的表型 衰老比永生占优势，另外还有一个细胞 融合，涉及不朽的人类细胞，定义了四个 无限除法的补群。微细胞融合 方法已经确定了与细胞衰老相关的基因的存在 B、C和D组，分别位于第4、1和7号染色体上。更多 最近，使用针对死亡蛋白的抗体，进行免疫染色 已经发现了区分正常细胞和永生细胞的模式，如 以及确定永生细胞与之互补的基团 分配。有趣的是，死亡模式恢复到正常模式 微细胞杂交体中表现出增殖丧失的细胞 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。)我们还没有研究 导入人类4号染色体获得的微细胞杂交种 转化为分配给B组的永生细胞)。这项提议的目的是 因此，要确定特定亚细胞中的定位是否 隔室是造成这种染色差异的原因，而 导致观察到差异染色的分子机制。 研究结果将加深我们对相关机制的理解 细胞衰老和永生。

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.