Abstract
The generation of new blood vessels from the existing vasculature is a dynamic and complex mechanism known as angiogenesis. Angiogenesis occurs during the entire lifespan of vertebrates and participates in many physiological processes. Furthermore, angiogenesis is also actively involved in many human diseases and disorders, including cancer, obesity and infections. Several inter-connected molecular pathways regulate angiogenesis, and post-translational modifications, such as phosphorylation, ubiquitination and SUMOylation, tightly regulate these mechanisms and play a key role in the control of the process. Here, we describe in detail the roles of ubiquitination and SUMOylation in the regulation of angiogenesis.
Highlights
The growth of new blood vessels from the existing vasculature is a process known as angiogenesis (Carmeliet, 2003; Ucuzian et al, 2010)
It has been recently reported that VEGFR2 can be ubiquitinated and degraded in a VEGF-independent manner: in this case, the E1 ubiquitin-activating enzyme UBA1 controls the basal levels of VEGFR2 as well as its activity (Smith et al, 2017). These findings suggest that ubiquitination can independently regulate the availability of the VEGFR2 receptor during angiogenesis
These data indicate that SUMOylation inhibits VEGFR2-dependent angiogenesis (Fig. 18.2), suggesting that the balance between the SUMOylated and non-SUMOylated VEGFR2 dictates its activation during angiogenesis (Zhou et al, 2018)
Summary
The growth of new blood vessels from the existing vasculature is a process known as angiogenesis (Carmeliet, 2003; Ucuzian et al, 2010). Many diseases can promote de novo angiogenesis, a process known as pathological angiogenesis or neoangiogenesis In this regard, a well-known example is tumorigenesis-induced angiogenesis, during which hypoxic and starved cancer cells activate the molecular pathways involved in the formation of novel blood vessels, in order to supply nutrients and oxygen required for the tumour growth. Angiogenesis relays on several pathways that cooperate in order to regulate in a precise spatial and temporal order the process. In this context, post-translational modifications (PTMs) play a central role in the regulation of these events, influencing the activation and stability of many growth factors, membrane receptors and downstream signalling effector molecules. We will focus on the role of ubiquitination and SUMOylation in the regulation of angiogenesis
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