Stabilization of p53 and transactivation of its target genes in response to replication blockade.
Stabilization of p53 and transactivation of its target genes in response to replication blockade.
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p53 的稳定及其靶基因的反式激活以响应复制阻断。
DOI：
10.1038/sj.onc.1205889
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发表时间：
2002
期刊：
影响因子：
8
通讯作者：
Das,GokulM
中科院分区：
文献类型：
--
作者：
Nayak,BijayaK;Das,GokulM
尽管 p53 在 G1/G2 检查点中维持基因组完整性方面发挥着关键作用，但其在 S 期检查点中的作用尚不清楚。最近，有报道称，尽管 p53 在复制阻断期间稳定，但其转录受损。然而，这种现象背后的机制尚不清楚。目前的研究表明，p53 会积累并反式激活其靶基因，例如 p21、gadd45 和 bax，以响应正常细胞和癌细胞中的复制阻断。在缺乏p53的细胞中类似条件下缺乏转录激活表明复制阻断期间p53靶基因的激活确实是p53依赖性的。此外，响应羟基脲和阿非迪霉素复制阻断的p21反式激活与响应电离辐射的反式激活类似，只是后者比对复制阻断的响应更直接。这些发现表明转录活性 p53 因复制阻断而受损并不是普遍现象。
Although it is clear that p53 plays a pivotal role in G1/G2 checkpoints to conserve genomic integrity, its role in S phase checkpoint is less well understood. Recently, it has been reported that p53 is transcriptionally impaired even though it is stabilized during replication blockade. However, the mechanisms underlying this phenomenon are not known. In the present study, it has been shown that p53 accumulates and transactivates its target genes such as p21, gadd45 and bax in response to replication blockade in normal and cancer cells. Lack of transcriptional activation under similar conditions in cells lacking p53 shows that p53-target gene activation during replication blockade is indeed p53-dependent. Further, transactivation of p21 in response to replication blockade by hydroxyurea and aphidicolin is similar to that in response to ionizing radiation except that the latter is more immediate compared to the response to replication blockade. These findings suggest that impairment of transcriptionally active p53 in response to replication blockade is not a general phenomenon.