ΔN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53
ΔN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53
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DOI：
10.1038/sj.onc.1205874
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发表时间：
2002-10-03
期刊：
影响因子：
8
通讯作者：
Hainaut, P
中科院分区：
文献类型：
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作者：
Courtois, S;Verhaegh, G;Hainaut, P
肿瘤抑制蛋白p53作为53kd的主要异构体普遍表达，但已经观察到几种低分子量的形式。在这里，我们描述了一个新的异构体，delta -p53，由密码子40的内部翻译起始产生，缺乏n端第一反激活结构域。该异构体具有受损的转录激活能力，并且不与p53调节蛋白Mdm2复合。此外，DeltaN-p53与全长p53 （FL-p53）寡聚并负调控其转录和生长抑制活性。与缺乏Mdm2结合相一致，DeltaN-p53不会在dna损伤的反应中积累，这表明该亚型不参与对基因毒性应激的反应。然而，在表达野生型p53的血清饥饿细胞中，在血清刺激后同步进展到S期时，DeltaN-p53成为主要的p53形式。这些结果表明，在细胞周期进程中，DeltaN-p53可能作为p53的短暂负调节因子发挥作用。
The tumor suppressor protein p53 is ubiquitously expressed as a major isoform of 53 kD, but several forms of lower molecular weight have been observed. Here, we describe a new isoform, DeltaN-p53, produced by internal initiation of translation at codon 40 and lacking the N-terminal first transactivation domain. This isoform has impaired transcriptional activation capacity, and does not complex with the p53 regulatory protein Mdm2. Furthermore, DeltaN-p53 oligomerizes with full-length p53 (FL-p53) and negatively regulates its transcriptional and growth-suppressive activities. Consistent with the lack of Mdm2 binding, DeltaN-p53 does not accumulate in response to DNA-damage, suggesting that this isoform is not involved in the response to genotoxic stress. However, in serum-starved cells expressing wild-type p53, DeltaN-p53 becomes the predominant p53 form during the synchronous progression into S phase after serum stimulation. These results suggest that DeltaN-p53 may play a role as a transient, negative regulator of p53 during cell cycle progression.