Seminar

Oncogenic and anti-oncogenic roles of E2F transcription factors

Ana Zubiaga, PhD

Dr. Ana Zubiaga is a Professor in the Department of Genetics, Physical Anthropology and Animal Physiology at the University of the Basque Country, UPV/EHU, since 1995. Her research interests lie in the area of cancer biology, particularly the Retinoblastoma-RB/E2F pathway and its role in cell fate decisions. E2F transcription factors (E2F1-8), downstream effectors of RB tumor suppressor, are key regulators of cell cycle progression. They control the expression of a wide range of transcriptional targets involved in DNA replication and repair, cell cycle progression, apoptosis, or differentiation, which underscores their relevance in cell fate regulatory networks. Functional inactivation of RB and aberrant E2F activity are common features of tumor cells. Thus, E2F targeting is being explored as a therapeutic strategy in cancer. However, the physiologic and pathologic roles played by individual E2F family members are still largely unknown, and Ana Zubiaga’s lab uses cellular and animal genetic models to understand them. Their recent studies show that loss of E2F activity does not impair cellular proliferation. Instead, it is associated with increased genomic instability and oncogenic potential in normal differentiating cells. Furthermore, DNA repair activity in tumor cells is increased upon depletion of some E2F members. These findings raise the possibility that systemic administration of pan-E2F inhibitors might have undesired outcomes that could have implications for cancer therapy.