Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer
Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer
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DOI：
10.1093/jnci/djh292
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发表时间：
2004-11-17
影响因子：
10.3
通讯作者：
Villalona-Calero, MA
中科院分区：
文献类型：
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作者：
Duan, WR;Gao, L;Villalona-Calero, MA
p53功能的维持对于正常细胞生长和发育是重要的，并且p53功能的丧失直接有助于恶性肿瘤的发展。最近发现的Pirh 2蛋白是一种泛素-蛋白连接酶，通过靶向p53进行降解，从而通过活性负调控p53。为了确定Pirh 2如何介导肺肿瘤发生，我们使用免疫印迹分析和免疫组织化学评估了人和小鼠肺肿瘤样品和配对正常肺组织中的Pirh 2表达。Pirh 2蛋白表达在32例人肺肿瘤中有27例（84%）高于匹配的正常肺组织，在评估的15例小鼠肺肿瘤中有14例。此外，p53蛋白在小鼠肺肿瘤中比在正常组织中更泛素化，并且总体p53表达低于正常组织。这些结果与Pirh 2表达增加通过降低p53活性影响肺肿瘤发生的假设一致。据我们所知，这是人类和小鼠肿瘤中Pirh 2表达改变的首次描述。
Maintenance of p53 function is important for normal cell growth and development, and loss of p53 function contributes directly to malignant tumor development. The recently discovered Pirh2 protein is an ubiquitin-protein ligase that negatively regulates p53 through activity by targeting it for degradation. To determine how Pirh2 may mediate lung tumorigenesis, we evaluated Pirh2 expression in human and mouse lung tumor samples and paired normal lung tissues using immunoblot analysis and immunohistochemistry. Pirh2 protein expression was higher in 27 (84%) of 32 human lung neoplasms than in matched normal lung tissue and in 14 of 15 mouse lung tumors evaluated. In addition, p53 protein was more ubiquitinated in the mouse lung tumors than in normal tissue, and overall p53 expression was lower than that in normal tissue. These results are consistent with the hypothesis that increased Pirh2 expression affects lung tumorigenesis by reducing p53 activity. To our knowledge, this is the first description of altered Pirh2 expression in human and mouse tumors.