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.
Stefan Duensing,Lily Y. Lee,Anette Duensing,John R. Basile,Siribang-on Piboonniyom,Sonia L. Gonzalez,Christopher P. Crum,Karl Münger +7 more
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TLDR
It is shown 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.Abstract:
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.read more
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Human papillomavirus oncoproteins: pathways to transformation
TL;DR: Understanding how HPV oncoproteins modify these activities provides novel insights into the basic mechanisms of oncogenesis, which are crucial regulators of cell cycle progression, telomere maintenance, apoptosis and chromosomal stability.
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Mechanisms of Human Papillomavirus-Induced Oncogenesis
Karl Münger,Amy Baldwin,Kirsten M Edwards,Hiroyuki Hayakawa,Christine L. Nguyen,Michael Owens,Miranda Grace,Kyung-Won Huh +7 more
TL;DR: Papillomaviruses are small nonenveloped viruses with 55-nm-diameter icosahedral capsids that contain double-stranded DNA genomes of approximately 8,000 bp that infect squamous epithelia and cause the generation of warts.
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Centrosome aberrations: cause or consequence of cancer progression?
TL;DR: Many human tumours show centrosome aberrations, indicating an underlying deregulation of centrosomes structure, duplication or segregation, and what impact do they have on the generation of invasive, genetically unbalanced cells during cancer progression?
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Human papillomavirus immortalization and transformation functions.
Karl Münger,Peter M. Howley +1 more
TL;DR: The state of the field at the time of the 19th International Papillomavirus Workshop in September 2001 with respect to the HPV encoded oncoproteins is reviewed.
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Nucleotide deficiency promotes genomic instability in early stages of cancer development.
Assaf C. Bester,Maayan Roniger,Yifat S. Oren,Michael M. Im,Dan Sarni,Malka Chaoat,Aaron Bensimon,Gideon Zamir,Donna S. Shewach,Batsheva Kerem +9 more
TL;DR: The replication dynamics in cells in which a regulator of S phase entry and cell proliferation, the Rb-E2F pathway, is aberrantly activated are studied to suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability.
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