The Human Papillomavirus (HPV) 16 E2 Protein Induces Apoptosis in the Absence of Other HPV Proteins and via a p53-dependent Pathway*
The Human Papillomavirus (HPV) 16 E2 Protein Induces Apoptosis in the Absence of Other HPV Proteins and via a p53-dependent Pathway*
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DOI：
10.1074/jbc.275.1.87
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发表时间：
2000-01
期刊：
影响因子：
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通讯作者：
K. Webster;Joanna L. Parish;Maya Pandya;P. Stern;A. Clarke;K. Gaston
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文献类型：
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作者：
K. Webster;Joanna L. Parish;Maya Pandya;P. Stern;A. Clarke;K. Gaston
人乳头瘤病毒（HPV）E2蛋白调节病毒基因表达，也是病毒复制所需的。HPV转化的细胞通常含有染色体整合的HPV基因组拷贝，其中病毒E2基因被破坏。我们先前已经表明，在HPV 16转化的细胞中HPV 16 E2蛋白的再表达通过凋亡导致细胞死亡。在这里，我们表明，HPV 16 E2蛋白可以诱导细胞凋亡的HPV转化和非HPV转化的细胞系。E2诱导的细胞凋亡被p53的反式显性负突变体或HPV 16 E6蛋白的过表达所消除，但被野生型p53的过表达所增加。我们发现，突变，阻止E2的DNA结合活性不损害这种蛋白质诱导细胞凋亡的能力。相反，从E2二聚体去除两个N-末端结构域完全阻断E2诱导的细胞死亡。野生型E2和N-末端缺失的E2蛋白之间形成的异源二聚体也不能诱导细胞死亡。我们的数据表明，无论是DNA结合活性的E2或其他HPV蛋白是必需的诱导凋亡的E2和E2诱导的细胞死亡发生通过p53依赖性途径。
The human papillomavirus (HPV) E2 protein regulates viral gene expression and is also required for viral replication. HPV-transformed cells often contain chromosomally integrated copies of the HPV genome in which the viral E2 gene is disrupted. We have shown previously that re-expression of the HPV 16 E2 protein in HPV 16-transformed cells results in cell death via apoptosis. Here we show that the HPV 16 E2 protein can induce apoptosis in both HPV-transformed and non-HPV-transformed cell lines. E2-induced apoptosis is abrogated by a trans-dominant negative mutant of p53 or by overexpression of the HPV 16 E6 protein, but is increased by overexpression of wild-type p53. We show that mutations that block the DNA binding activity of E2 do not impair the ability of this protein to induce apoptosis. In contrast, removal of both N-terminal domains from the E2 dimer completely blocks E2-induced cell death. Heterodimers formed between wild-type E2 and N-terminally deleted E2 proteins also fail to induce cell death. Our data suggest that neither the DNA binding activity of E2 nor other HPV proteins are required for the induction of apoptosis by E2 and that E2-induced cell death occurs via a p53-dependent pathway.