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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