El eje Myc-Cdk1-p27 en proliferación y control de la diferenciación

Abstract

MYC is the first oncogenic transcription factor described and it is found deregulated in approximately 70% of human tumors. MYC regulates a large amount of biological processes. We have focused our work in MYC regulation of cell cycle progression and differentiation. In the first part of this thesis work we have described a new mechanism though which MYC induces p27 degradation (a cell cycle inhibitor) through the activation of Cdk1. This mechanism is of special interest due to the opposite correlation between high MYC levels and low p27 levels found in many tumors, which has been considered as poor prognosis. On the other hand, in the second part of this thesis work we have focused on the inhibition of the erythroid differentiation mediated by MYC. We described that this mechanism is independent of the MXD family of proteins (considered MYC antagonists and implicated in several differentiation proceses) as well as independent of the proliferation arrest that the cells undergo during the eryhtroid differentiation process.