A ROLE FOR BOTH RB AND P53 IN THE REGULATION OF HUMAN CELLULAR SENESCENCE

A ROLE FOR BOTH RB AND P53 IN THE REGULATION OF HUMAN CELLULAR SENESCENCE
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DOI:
10.1016/0014-4827(91)90453-2
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发表时间:
1991-09-01
影响因子:
3.7
通讯作者:
WRIGHT, WE
WRIGHT, WE
中科院分区:
医学3区
文献类型:
--
作者:
SHAY, JW;PEREIRASMITH, OM;WRIGHT, WE

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我们提出了 RB 和 p53 蛋白可能参与细胞衰老调节的证据。用诱导型 SV40 T 抗原永生化的人成纤维细胞在 T 抗原去诱导后变得衰老。表达完整 T 抗原替代来源的质粒可恢复增殖,但缺乏 RB 或 p53 结合域的 T 抗原缺失突变体则无法做到这一点。同样,腺病毒 E1A + E1B 或人乳头瘤病毒 E6 + E7 基因的组合能够取代 T 抗原功能并允许细胞增殖,而单个基因则不能。这些结果根据体外细胞衰老逃逸的两阶段模型进行了讨论。
We present evidence for the possible involvement of both the RB and p53 proteins in the regulation of cellular senescence. Human fibroblasts immortalized with an inducible SV40 T-antigen become senescent following the de-induction of T-antigen. Plasmids expressing an alternative source of intact T-antigen restore proliferation but T-antigen deletion mutants lacking either the RB or p53 binding domains are unable to do so. Similarly, combinations of adenovirus E1A + E1B or human papillomavirus E6 + E7 genes are able to replace T-antigen functions and permit cell proliferation, whereas the individual genes do not. These results are discussed in terms of a two-stage model for the escape fromin vitrocellular senescence.