Research Groups
Tumour Virology
Research Interests and Description
Research Interests
Molecular biology of Human Papillomaviruses.
Description of Research
Human Papillomaviruses (HPVs) are the causative agents of a number of human tumours, including cervical cancer, which is the major cause of cancer related death in women in many parts of the developing world. The development of these tumours requires the action of two viral oncoproteins, E6 and E7: understanding the mechanism of action of these two HPV gene products is one of the major aims of the laboratory. The work has focused on identifying the cellular targets of the viral oncoproteins and we are now dissecting the effects of these proteins upon important cellular regulatory pathways. Current major interests include the cell polarity regulators Discs Large and Scribble, both of which are potential tumour suppressor proteins. Indeed, loss of Scribble expression results in increased tumour invasive potential (see Figure). The laboratory is also aiming to develop novel therapeutics directed against E6 and studies are also in progress aiming to more fully understand the function of the E6 associated ubiquitin ligase (E6AP). Recent work has also begun to investigate the mechanisms by which HPVs enter the target cell, with emphasis being placed on dissecting the function of the minor capsid protein L2. These studies have used proteomic approaches to identify critical cellular pathways that facilitate viral infection.
The Group’s studies invariably also require extensive molecular cell biological analyses of the viral target proteins, since in many cases these are themselves, only poorly understood. Thus, as has been seen with other DNA Tumour Virus models, HPV research offers unique insights into the processes affecting diverse and critical aspects of cell biology.
Recent Publications
Kranjec, C., Banks, L. 2011. A systematic analysis of human papillomavirus (HPV) E6 PDZ substrates identifies MAGI-1 as a major target of HPV type 16 (HPV-16) and HPV-18 whose loss accompanies disruption of tight junctions. J. Virol. 85, 1757-1764 PubMed link
Tomaic, V., Pim, D., Thomas, M., Massimi, P., Myers, M.P., Banks,
L. 2011. Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin
ligase complex by the HECT domain-containing protein EDD. J. Virol. 85,
3120-3127 PubMed link
Nagasaka, K., Pim, D., Massimi,
P., Thomas, M., Tomaic, V., Subbaiah, V., Kranjec, C., Nakagawa, S., Yano, T.,
Taketani, Y., Myers, M., Banks, L. 2010. The cell polarity regulator hScrib
controls ERK activation through a KIM site-dependent interaction. Oncogene 29, 5311-5321 PubMed link
Gammoh, N., Isaacson, E., Tomaic, V., Jackson, D., Doorbar, J., Banks, L. 2009. Inhibition of HPV-16 E7 oncogenic activity by HPV-16 E2. Oncogene 28, 2299-2304 PubMed link
Thomas, M., Narayan, N., Pim, D., Tomaic, V., Massimi, P., Nagasaka, K., Kranjec, C., Gammoh, N., Banks, L. 2008. Human papillomaviruses, cervical cancer and cell polarity. Oncogene 27, 6876-6877 PubMed link
Tomaic, V., Pim, D., Banks, L. 2009. The stability of the human papillomavirus E6 oncoprotein is E6AP dependent. Virology 393, 7-10 PubMed link
