The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle
The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle
复制标题
DOI：
10.1073/pnas.170093297
复制
发表时间：
2000-08-29
影响因子：
11.1
通讯作者：
Münger, K
中科院分区：
文献类型：
--
作者：
Duensing, S;Lee, LY;Münger, K
基因组完整性的丧失是许多人类恶性肿瘤的定义特征，包括人乳头瘤病毒（HPV）相关的浸润前和浸润性生殖器鳞状病变。在这里，我们表明，异常的中心体数目所造成的异常有丝分裂纺锤体极的形成是一个重要的机制，在占HPV相关的致癌染色体数目的改变。与我们在组织病理学标本中发现的相似，HPV-16 E6和E7癌蛋白协同诱导异常中心体数目、异常有丝分裂纺锤体极形成和基因组不稳定性。低风险HPV-6 E6和E7蛋白不诱导这种异常。然而HPV-16 E6癌蛋白对中心体数目没有直接影响，HPV-16 E7迅速诱导异常中心体复制。因此，我们的研究结果表明，HPV-16 E7诱导中心体相关的有丝分裂障碍，增强了HPV-16 E6的模型。
Loss of genomic integrity is a defining feature of many human malignancies, including human papillomavirus (HPV)-associated preinvasive and invasive genital squamous lesions. Here we show that aberrant mitotic spindle pole formation caused by abnormal centrosome numbers represents an important mechanism in accounting for numeric chromosomal alterations in HPV-associated carcinogenesis. Similar to what we found in histopathological specimens, HPV-16 E6 and E7 oncoproteins cooperate to induce abnormal centrosome numbers, aberrant mitotic spindle pole formation, and genomic instability. The low-risk HPV-6 E6 and E7 proteins did not induce such abnormalities. Whereas the HPV-16 E6 oncoprotein has no immediate effects on centrosome numbers, HPV-16 E7 rapidly induces abnormal centrosome duplication. Thus our results suggest a model whereby HPV-16 E7 induces centrosome-related mitotic disturbances that are potentiated by HPV-16 E6.