Chapter Eight - Ubiquitin-Mediated Regulation of Cellular Responses to Vascular Endothelial Growth Factors

Vascular endothelial growth factors (VEGFs) bind receptor tyrosine kinases (VEGFRs) to regulate vascular and lymphatic development and homeostasis. Such interactions are also implicated in pathological conditions ranging from cancer to heart disease. Increasingly, it is evident that ubiquitination plays a central role in regulating VEGFR function and the cellular response to VEGFs. E1, E2, and E3 ubiquitination enzymes deliver ubiquitin-specific modifications to protein substrates but there is much debate on the exact enzymes involved. The deubiquitinase (DUB) enzymes remove such modifications and are attracting increasing interest as potential therapeutic targets in a host of different disease states. Understanding how these enzyme families regulate VEGFR function in different cells and tissues is a major challenge. An understanding of the fundamental mechanisms underlying such biochemical regulation is needed for providing new therapeutics that target diseases such as cancer and heart disease.