Human papillomavirus type 8 oncoproteins E6 and E7 cooperate in downregulation of the cellular checkpoint kinase-1

International Journal of Cancer. Journal International Du Cancer
Baki AkgülMartin Hufbauer

Abstract

Human papillomavirus 8 (HPV8) is associated with the development of squamous cell carcinoma (SCC) of the skin. HPV-infected keratinocytes are able to override normal checkpoint control mechanisms and sustain cell cycle activity, allowing for synthesis of cellular proteins necessary for viral genome amplification. To study how HPV8 may disrupt cell cycle control, we analyzed the impact of HPV8 early gene expression on one of the key regulators of cell cycle and DNA damage response, checkpoint kinase-1 (CHK1). We found that expression of E1, E1̂E4, E2, E6 or E7 individually did not affect CHK1; however, keratinocytes expressing the complete early genome region (CER) of HPV8 showed a profound loss of CHK1 protein levels, that proved to be mediated by E6E7 co-expression. Neither CHK1 promoter regulation nor the ubiquitin-proteasome pathway are involved in HPV8-mediated CHK1 repression. However, CHK1 protein repression in organotypic skin cultures was paralleled by downregulation of the autophagy marker LC3B. Treatment of HPV8-CER expressing cells with the autophagy inhibitor Bafilomycin A1 rescued CHK1 expression and led to LC3B accumulation. Taken together, our data implicate that CHK1 autophagic degradation is enhanced by HPV8, w...Continue Reading

References

Oct 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Hui ZhaoHelen Piwnica-Worms
Apr 5, 2003·The Journal of Biological Chemistry·Zhan XiaoHaiying Zhang
Mar 1, 2005·Cancer Research·Inke Diana SchaperHerbert Pfister
Jun 29, 2005·The Journal of Investigative Dermatology·Soenke Jan WeissenbornUlrike Wieland
Sep 3, 2005·Molecular Cell·You-Wei ZhangRobert T Abraham
Jan 2, 2007·Apoptosis : an International Journal on Programmed Cell Death·Sabrina LeverrierAlan Storey
Apr 5, 2011·Journal of Dermatological Science·Daliborka LazićBaki Akgül
Jul 19, 2012·PLoS Pathogens·Nicholas A WallaceDenise A Galloway
Dec 6, 2012·The Journal of Biological Chemistry·Lei QiangYu-Ying He
Nov 20, 2014·International Journal of Cancer. Journal International Du Cancer·Amy HollowayAlan Storey
Apr 17, 2015·Nature Communications·Caroline ParkAna Maria Cuervo
May 27, 2015·Viruses·Caleb C McKinneyAlison A McBride
Aug 8, 2015·Viruses·Jennifer Biryukov, Craig Meyers
Sep 24, 2015·Current Opinion in Virology·Denise A Galloway, Laimonis A Laimins
Mar 30, 2016·The Journal of Investigative Dermatology·Olufolake AkinduroDaniele Bergamaschi
Jul 15, 2017·Viruses·Martin Hufbauer, Baki Akgül
Dec 1, 2017·Frontiers in Microbiology·Sebastian O Wendel, Nicholas A Wallace

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.