Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control Wednesday Speaker Abstracts

The Oncoproteins of Human Papillomaviruses: Instances of Viral Strategies for Hijacking of Host Motifs Gilles Trave . IREBS, UMR 7242 CNRS, Illkirch, France. Papillomaviruses are small oncogenic DNA viruses infecting the epithelia of mammals, birds and reptiles. "High-risk" papillomaviruses (hrm-HPVs) are the main cause for cervical cancer and are also often involved in head and neck cancers and in some cutaneous tumours. The oncogenic properties of papillomaviruses are mainly due to two "oncoproteins", E6 and E7, which promote proliferation and immortalisation and perturbate the adhesion properties of the infected cells. E6 and E7 proteins bind to large numbers of target proteins controlling cell proliferation (Rb, cyclins...), cell adhesion (PDZ domain proteins), protein degradation (E6AP, Cullin) and cell death (p53, BAK, Bax...). E6 and E7 proteins possess 150 and 100 residues, respectively. Interestingly, E6 and E7 mainly act by hijacking Small Linear Motifs (SLiMs) which normally mediate protein-protein interaction networks within the host. Both E6 and E7 extensively employ motif mimicry strategies, as observed for many other viruses (see review by Davey et al., Trends Biochem Sci. 2011). In particular, E7 contains a LxCxE motif which binds to diverse members of the Rb family, while E6 contains a C-terminal motif recognizing PDZ domains. E6 also employs a less usual strategy, which consists in capturing within its target host proteins acidic helical motifs containing the consensus LxxLL, which include some "LD motifs" found in various proteins involved in cell adhesion and polarity control. The LxxLL and PDZ hijacking properties of E6 and their biological implications will be discussed in detail in the light of recent structural and functional data obtained in our laboratory.

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