My laboratory is focused on the mechanisms controlling growth and cell cycle of the mammalian cell. They respond to perturbations like replication errors or DNA damage by inducing cell cycle arrest, senescence, or apoptosis.  Dysfunction of these mechanisms often results in the malignant transformation of a cell and the development of cancer. E2F is a family of transcription factors that integrate cell-cycle progression with transcription through cyclical interactions with important cell cycle regulators.

We have recently identified and characterized a protein that we called EAPP (E2F Associated PhosphoProtein). EAPP interacts with E2F1-3, comprising the activator group of E2F proteins, and modulates E2F-dependent transcription. Tumour cells often overexpress EAPP, indicating that it confers a selective advantage to these cells. EAPP levels increase upon DNA damage and higher EAPP levels seem to protect cells from apoptosis. This protection can also be achieved by ectopic expression of EAPP and correlates with an increased number of cells in G1 phase and an upregulation of p21. Increased p21 inhibits cyclin/cdk activity which is required for cell cycle progression, but has also interferes with apoptosis. The RNAi-mediated knock down of p21 reduces the anti-apoptotic activities of overexpressed EAPP. This suggests that p21 at least in part mediates this activity of EAPP.

EAPP stimulates p21 expression by binding to its promoter and seems to be required for the assembly of the transcription initiation. The knock down of EAPP facilitates apoptosis and goes along with reduced p21.

Our findings suggest that EAPP is indispensable for the survival of a cell.  The required amount of EAPP seems to depend on the environmental conditions. Preliminary evidence suggests that the role of EAPP in transcription is not limited to the p21 promoter. Active promoters are occupied by multiple types of complexes and EAPP seems to be an important component of at least some of them. Lowering EAPP levels influences the expression of some of the genes examined including important cell-cycle regulators. To examine which genes are influenced by EAPP and to scrutinize the biochemical details of its activity will be focus of future.