Open AccessThe 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
Author(s) -
Stefan Duensing,
Lily Y. Lee,
Anette Duensing,
John R. Basile,
Siribang-on Piboonniyom,
Sonia L. Gonzalez,
Christopher P. Crum,
Karl Münger
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.170093297
Subject(s) - centrosome , mitosis , genome instability , biology , carcinogenesis , chromosome instability , multipolar spindles , spindle apparatus , microbiology and biotechnology , centrosome cycle , gene duplication , spindle pole body , cancer research , chromosome segregation , cell division , cell cycle , chromosome , genetics , cell , gene , dna damage , dna
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.