Functional association between Wwox tumor suppressor protein and p73, a p53 homolog
Functional association between Wwox tumor suppressor protein and p73, a p53 homolog
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DOI：
10.1073/pnas.0400805101
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发表时间：
2004-03-30
影响因子：
11.1
通讯作者：
Croce, CM
中科院分区：
文献类型：
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作者：
Aqeilan, RI;Pekarsky, Y;Croce, CM
WWOX基因是最近克隆的肿瘤抑制基因，跨越FRA16D脆弱区。 Wwox 蛋白含有两个 WW 结构域，通常已知它们介导蛋白质-蛋白质相互作用。在这里，我们展示了 Wwox 通过其第一个 WW 结构域与 p53 同源物 p73 进行物理相互作用。酪氨酸激酶 Src 使第一个 WW 结构域中酪氨酸 33 处的 Wwox 磷酸化，并增强其与 p73 的结合。我们的结果进一步证明 Wwox 表达触发核 p73 重新分布到细胞质，从而抑制其转录活性。此外，我们发现细胞质 p73 有助于 Wwox 的促凋亡活性。我们的研究结果揭示了 p73 和 Wwox 肿瘤抑制蛋白之间的功能串扰。
The WWOX gene is a recently cloned tumor suppressor gene that spans the FRA16D fragile region. Wwox protein contains two WW domains that are generally known to mediate protein-protein interaction. Here we show that Wwox physically interacts via its first WW domain with the p53 homolog, p73. The tyrosine kinase, Src, phosphorylates Wwox at tyrosine 33 in the first WW domain and enhances its binding to p73. Our results further demonstrate that Wwox expression triggers redistribution of nuclear p73 to the cytoplasm and, hence, suppresses its transcriptional activity. In addition, we show that cytoplasmic p73 contributes to the proapoptotic activity of Wwox. Our findings reveal a functional cross-talk between p73 and Wwox tumor suppressor protein.