Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis.-猫眼课题宝

DOI：

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发表时间：

1994-12

期刊：

Oncogene

影响因子：

8

通讯作者：

中科院分区：

医学1区

文献类型：

--

作者：

Qimin Zhan;Sajan Fan;Insoo Bae;C. Guillouf;D. Liebermann;Patrick M. O'Connor;A. Fornace

dna损伤剂如电离辐射（IR）可激活肿瘤抑制因子p53，在某些情况下可导致细胞凋亡。不表达内源性肿瘤抑制基因p53的M1细胞在激活对温度敏感的p53转基因后会发生凋亡，其中已证明bax是p53的重要介质，是p53的靶基因（Selvakumaran等人，Oncogene 9, 1791- 8,1994）。由于p53在IR激活后可以作为转录因子发挥作用，因此在一组具有p53状态的人类细胞中检查了对这种应激的遗传反应。与p53调控基因gadd45一样，bax在p53 wt（野生型）人髓系ML-1中被快速诱导，而在缺乏功能性p53的细胞中不被诱导。然而，与其他p53调控基因不同，bax仅在p53 wt细胞中被诱导，而IR也会引发细胞凋亡。在与bax功能相反的bcl2的情况下，IR后ML-1细胞中的mRNA水平降低。因此，bax似乎是一种独特的p53调控基因，它的IR诱导不仅需要p53的功能，而且需要细胞凋亡“熟练”。

DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis "proficient."