Elevated expression and activity of mitotic regulatory proteins in human papillomavirus-immortalized keratinocytes.
Elevated expression and activity of mitotic regulatory proteins in human papillomavirus-immortalized keratinocytes.
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发表时间：
1994-02
期刊：
影响因子：
8
通讯作者：
K. Steinmann;X. Pei;H. Stöppler;R. Schlegel
中科院分区：
文献类型：
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作者：
K. Steinmann;X. Pei;H. Stöppler;R. Schlegel
人乳头瘤病毒(HPV)16型和18型的E6和E7蛋白在宫颈癌细胞系中表达，并能使原代人类角质形成细胞永生化。由于E6/E7基因的表达可导致人类原代细胞有丝分裂缺陷和核型不稳定，我们研究了这些病毒癌蛋白对有丝分裂调节蛋白表达和活性的影响。与正常亲本细胞相比，由整个基因组或仅由HPV16和18型E6/E7基因永生化的原代人角质形成细胞的p34cdc2、细胞周期蛋白B和细胞周期蛋白A的丰度增加了5-20倍。来自相同单一捐赠者的正常和永生化细胞的结果与来自混合捐赠者培养的结果相似。蛋白质水平的增加没有相应的mRNA增加，这表明翻译和/或翻译后控制发生了变化。与这些调节蛋白相关的组蛋白H1激酶活性也升高，但程度低于蛋白质水平。由于p34cdc2、Cyclin B和Cyclin A调节有丝分裂的进入和退出，这些蛋白的表达和活性增加可能导致与HPV诱导的永生化相关的有丝分裂缺陷和染色体畸形。
The E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18 are expressed in cell lines derived from cervical cancers and can immortalize primary human keratinocytes. Since expression of E6/E7 has been shown to induce mitotic defects and karyotype instability in primary human cells, we investigated the effect of these viral oncoproteins on the expression and activity of mitotic regulatory proteins. Primary human keratinocytes immortalized by the entire genome or by only the E6/E7 genes of HPV types 16 and 18 displayed 5- to 20-fold increases in the abundance of p34cdc2, cyclin B and cyclin A when compared with normal parental cells. Results obtained from normal and immortalized cells that were derived from identical single donors were similar to those from mixed donor cultures. Increased protein levels were achieved without corresponding increases in mRNA, indicating alterations in translational and/or post-translational control. The histone H1 kinase activities associated with these regulatory proteins were also elevated, but to a lesser extent than the protein levels. Because p34cdc2, cyclin B and cyclin A regulate the entry into and exit from mitosis, increased expression and activity of these proteins could contribute to the mitotic defects and chromosomal aberrations associated with HPV-induced immortalization.