title: The ubiquitin-proteasome system meets angiogenesis.
abstract: A strict physiological balance between endogenous proangiogenic and antiangiogenic factors controls endothelial cell functions, such that endothelial cell growth is normally restrained. However, in pathologic angiogenesis, a shift occurs in the balance of regulators, favoring endothelial growth. Much of the control of angiogenic events is instigated through hypoxia-induced VEGF expression. The ubiquitin-proteasome system (UPS) plays a central role in fine-tuning the functions of core proangiogenic proteins, including VEGF, VEGFR-2, angiogenic signaling proteins (e.g., the PLCγ1 and PI3 kinase/AKT pathways), and other non-VEGF angiogenic pathways. The emerging mechanisms by which ubiquitin modification of angiogenic proteins control angiogenesis involve both proteolytic and nonproteolytic functions. Here, I review recent advances that link the UPS to regulation of angiogenesis and highlight the potential therapeutic value of the UPS in angiogenesis-associated diseases.
authors.affiliation: Department of Pathology, Boston University Medical Campus, 670 Albany St., Room 510, Boston, MA 02118, USA. nrahimi@bu.edu
authors.forename: Nader
authors.initials: N
authors.lastname: Rahimi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042501:Angiogenic Proteins / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex