Peptide binding to Geminin and inhibitory for DNA replication.
Peptide binding to Geminin and inhibitory for DNA replication.
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DOI：
10.1016/j.bbrc.2004.03.035
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发表时间：
2004-04
影响因子：
3.1
通讯作者：
Kenichi Yoshida;I. Inoue
中科院分区：
文献类型：
--
作者：
Kenichi Yoshida;I. Inoue
Geminin与Cdt 1结合，以确保DNA复制在细胞周期中只发生一次。为了鉴定与Geminin结合并由此修饰后者改变人癌细胞中DNA复制活性的能力的肽，我们在噬菌体文库淘选的连续循环中筛选随机肽的噬菌体展示文库，并发现一个与Geminin的31-111个氨基酸残基结合的肽序列。将该肽序列递送到HCT 116人结肠癌细胞的细胞核中导致BrdU掺入的抑制。这些结果为Geminin的功能提供了新的见解，并进一步验证了Geminin作为肿瘤治疗的潜在靶点。
Geminin binds to Cdt1 to ensure that DNA replication occurs only once during the cell cycle. To identify the peptide that binds to Geminin and thereby modifies the latter’s ability to alter the DNA replication activity in human cancer cells, we screened a phage display library of random peptides in successive cycles of phage library panning and found one peptide sequence that bound to the 31–111 amino acid residues of Geminin. Delivery of this peptide sequence into the nucleus of HCT116 human colon cancer cells resulted in the suppression of BrdU incorporation. These results provide new insights into the function of Geminin and further validate Geminin as a potential therapeutic target in tumors.