Regulation of the Ets transcription factor Tel

Abstract

In this thesis we report novel studies on the molecular regulation of the transcriptional repressor Tel (Translocation Ets Leukemia). The work in this thesis is presented as follows: Chapter 1 is an introduction which summarizes the literature about Tel and its Drosophila orthologue Yan as it was known prior to the work presented here. Chapter 2 shows that Tel is modified by SUMO (Small Ubiquitin-like Modifier) on the highly conserved lysine 11 (K11), which serves to inhibit DNA binding of Tel. Chapter 3 describes the regulation of Tel and Yan by the F-box protein Fbl6, which mediates ubiquitination and subsequent degradation of Tel/Yan. Chapter 4 reports that Tel regulates angiogenesis through recruitment of the generic corepressor C-terminal Binding Protein (CtBP). This complex integrates intracellular Vascular Endothelial Growth Factor (VEGF) signaling and intercellular Delta-like 4 (Dll4)/Notch signaling. The impact of these findings is discussed in the general discussion in Chapter 5. Taken together the work in this thesis provides significant advances in the molecular details of Tel regulation. Furthermore, the work in chapter 4 should be of considerable importance to the field of angiogenesis.