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The objective consists in understanding how the post -translational regulation of p VHL is likely to influence its activity and function . In addition to its action as an E3 ligase , several alternative “non-canonical” functions of pVHL have been identified. The different approaches that we propose to develop will contribute to the elucidation of pVHL tumor suppressor function by evaluating how the modifications modulate its activit y during tumorigenesis by (1) modification of the cell cycle progression (2) the recruitment of protein partners, (3) by acting on the microtubules network.