期刊
MOLECULAR CANCER THERAPEUTICS
卷 11, 期 3, 页码 538-548出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-11-0555
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- National Eye Institute, National Institutes of Health
- Department of Pathology, Boston University
- Massachusetts Lions Foundation
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 PLC gamma(1) 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. (C) 2012 AACR.
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