The Ubiquitin-Proteasome System Meets Angiogenesis
- 1 March 2012
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 11 (3), 538-548
- https://doi.org/10.1158/1535-7163.mct-11-0555
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. Mol Cancer Ther; 11(3); 538–48. ©2012 AACR.Keywords
This publication has 101 references indexed in Scilit:
- Molecular mechanisms and clinical applications of angiogenesisNature, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Assembly, structure, and function of the 26S proteasomeTrends in Cell Biology, 2010
- Phosphatidylinositol 3-Kinase: The OncoproteinCurrent Topics in Microbiology and Immunology, 2010
- A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery developmentDevelopmental Biology, 2009
- Origin and function of ubiquitin-like proteinsNature, 2009
- Jade-1 inhibits Wnt signalling by ubiquitylating β-catenin and mediates Wnt pathway inhibition by pVHLNature, 2008
- Regulation of HIF-1α Stability through S-NitrosylationMolecular Cell, 2007
- Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesisExperimental Cell Research, 2006
- Patterns and Emerging Mechanisms of the Angiogenic Switch during TumorigenesisCell, 1996