Apoptosis; Cell Cycle; Chromatin; Cyclin-Dependent Kinase Inhibitor p21; DNA Damage; E2F Transcription Factors; Tumor Suppressor Protein p53
My laboratory is focused on the mechanisms controlling growth and cell cycle of the mammalian cell. Dysfunction of these mechanisms often results in the malignant transformation of a cell and the development of cancer.We have identified and characterized a protein that we called EAPP (E2F Associated PhosphoProtein). EAPP interacts with 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 protect cells from apoptosis. This results in an upregulation of p21 which inhibits cell cycle progression, but also interferes with apoptosis. Our findings suggest that EAPP is indispensable for the survival of a cell. The required amount of EAPP seems to depend on the cell type and environmental conditions. To examine which genes are influenced by EAPP and to scrutinize the biochemical details of its activity will be the focus of our future work.
Techniques, methods & infrastructure
- Standard molecular biology techniques
- tissue culture
- chromatin immunoprecipitation
- Andorfer, P., Schwarzmayr, L. & Rotheneder, H., 2011. EAPP modulates the activity of p21 and Chk2. Cell Cycle, 10(13), pp.2077-2082. Available at: http://dx.doi.org/10.4161/cc.10.13.16247.
- Andorfer, P. & Rotheneder, H., 2013. Regulation of the MDR1 promoter by E2F1 and EAPP. FEBS Letters, 587(10), pp.1504-1509. Available at: http://dx.doi.org/10.1016/j.febslet.2013.03.026.
- Haider, C. et al., 2013. Novel Inhibitors of Cyclin-Dependent Kinases Combat Hepatocellular Carcinoma without Inducing Chemoresistance. Molecular Cancer Therapeutics, 12(10), pp.1947-1957. Available at: http://dx.doi.org/10.1158/1535-7163.MCT-13-0263.
- Andorfer, P. & Rotheneder, H., 2011. EAPP: Gatekeeper at the crossroad of apoptosis and p21-mediated cell-cycle arrest. Oncogene, 30(23), pp.2679-2690. Available at: http://dx.doi.org/10.1038/onc.2010.639.
- Novy, M., 2005. EAPP, a Novel E2F Binding Protein That Modulates E2F-dependent Transcription. Molecular Biology of the Cell, 16(5), pp.2181-2190. Available at: http://dx.doi.org/10.1091/mbc.E04-11-0975.