Regulation of the cdk inhibitor, p27 Regulation des cdk inhibitor, p27

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The proposal aims at elucidating two aspects of regulation of the cell cycle inhibitor, p27kip1. First, we have identified a nucleoporin, mNup2, which interacts with p27 in a two-hybrid assay and in vitro. Using a loss-of-interaction screen, we have identified a specific point mutant of p27 that fails to interact with Nup2. In vivo, this mutant is not correctly localised in the nucleus but accumulates in the Cytosol. We now want to understand the functional implications of this interaction during the cell cycle. Second, we aim at understanding the negative regulation of p27 by Myc. We have found that Myc-induced inactivation of p27 is mediated by cyclin D2. The promoter of the cyclin D2 gene is repressed by Mad proteins and derepressed by a direct interaction with Myc/Max complexes. We now need to fully understand the role of cyclin D2 in cell cycle control and transformation by Myc.