Activation of p53-dependent responses in tumor cells treated with a PARC-interacting peptide.
Activation of p53-dependent responses in tumor cells treated with a PARC-interacting peptide.
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用 PARC 相互作用肽处理的肿瘤细胞中 p53 依赖性反应的激活。
DOI：
10.1016/j.bbrc.2008.01.093
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发表时间：
2008
影响因子：
3.1
通讯作者：
Raschellà,Giuseppe
中科院分区：
文献类型：
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作者：
Vitali,Roberta;Cesi,Vincenzo;Tanno,Barbara;Ferrari-Amorotti,Giovanna;Dominici,Carlo;Calabretta,Bruno;Raschellà,Giuseppe
我们用野生型细胞质P53检测了癌细胞中含有PARC相互作用区域的P53羧基末端多肽的活性。通过将其融合到TAT转导结构域(TAT-P53-C-TER多肽)来实现多肽递送。在双杂交试验中，P53的四聚结构域(TD)是与ParC结合的必要条件和充分条件。Tat-P53-C-ter多肽破坏了Parc-P53复合体。多肽处理引起P53核移位，P53依赖性基因表达改变，增强依托泊苷诱导的细胞凋亡。这些研究表明，ParC相互作用的多肽有望增强胞浆P53的肿瘤中P53依赖的细胞凋亡。
We tested the activity of a p53 carboxy-terminal peptide containing the PARC-interacting region in cancer cells with wild type cytoplasmic p53. Peptide delivery was achieved by fusing it to the TAT transduction domain (TAT-p53-C-ter peptide). In a two-hybrid assay, the tetramerization domain (TD) of p53 was necessary and sufficient to bind PARC. The TAT-p53-C-ter peptide disrupted the PARC–p53 complex. Peptide treatment caused p53 nuclear relocation, p53-dependent changes in gene expression and enhancement of etoposide-induced apoptosis. These studies suggest that PARC-interacting peptides are promising candidates for the enhancement of p53-dependent apoptosis in tumors with wt cytoplasmic p53.