Biotechnology and cell signalling (Jean-Luc Galzi)
(UMR 7242) > Genome integrity and tumor biology (Scientific coordination : Valérie Schreiber) > Nuclear signalling and cancererology > Research topics > Functions of HPV 16 E6
Functional analysis of HPV 16 E6 protein
In correlation with the structural work, the interactions between E6 and its cellular partners are studied at the functional level.
E6 interacts with the tumour suppressor p53 and the ubiquitin-ligase E6AP leading to the poly-ubiquitination and the degradation of p53. This activity is necessary for the oncogenic process. One of our projects is to dissect the molecular mechanism of p53 degradation (with emphasis on the binding sites and the role of post-translational modifications like phosphorylation). We also study the impact of E6-mediated degradation of p53 on cell death pathways (senescence or apoptosis) in HPV-induced tumours.
In addition, E6 contains a binding motif for a family of cellular domains called "PDZ" and thus targets several PDZ domain-containing proteins, an activity that is required for the oncogenic process. The PDZ/E6 interactions are analysed at the molecular and cellular level in particular in the context of cellular adhesion, polarity and proliferation.
An emergent project is the identification of all E6 and E7 interactions with ubiquitin ligases and deubiquitinases (DUB) in a global approach.
Molecular biology, cellular biology, cell imaging, phage display, protein/protein interaction assay (pulldown, IP, two hybrid system), proteomic approaches, RNA interference, kinases.
Collaboration : Y. Jacob, Unité des papillomavirus, Institut Pasteur, Paris
Contacts : Murielle Masson, Georges Orfanoudakis.