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lüll Hypoxia-induced angiogenesis during carcinogenesis Choi KS; Bae MK; Jeong JW; Moon HE; Kim KWJ Biochem Mol Biol 2003[Jan]; 36 (1): 120-7The formation of new blood vessels, angiogenesis, is an essential process during development and disease. Angiogenesis is well known as a crucial step in tumor growth and progression. Angiogenesis is induced by hypoxic conditions and regulated by the hypoxia-inducible factor 1 (HIF-1). The expression of HIF-1 correlates with hypoxia-induced angiogenesis as a result of the induction of the major HIF-1 target gene, vascular endothelial cell growth factor (VEGF). In this review, a brief overview of the mechanism of angiogenesis is discussed, focusing on the regulatory processes of the HIF-1 transcription factor. HIF-1 consists of a constitutively expressed HIF-1 beta (HIF-1beta) subunit and an oxygen-regulated HIF-1 alpha (HIF-1a) subunit. The stability and activity of HIF-1alpha are regulated by the interaction with various proteins, such as pVHL, p53, and p300/CBP as well as by post-translational modifications, hydroxylation, acetylation, and phosphorylation. It was recently reported that HIF-1alpha binds a co-activator of the AP-1 transcription factor, Jab-1, which inhibits the p53-dependent degradation of HIF-1 and enhances the transcriptional activity of HIF-1 and the subsequent VEGF expression under hypoxic conditions. ARD1 acetylates HIF-1alpha and stimulates pVHL-mediated ubiquitination of HIF-1alpha. With a growing knowledge of the molecular mechanisms in this field, novel strategies to prevent tumor angiogenesis can be developed, and from these, new anticancer therapies may arise.|*Neovascularization, Pathologic[MESH]|Animals[MESH]|Cell Transformation, Neoplastic/*metabolism[MESH]|DNA-Binding Proteins/*physiology[MESH]|Endothelial Growth Factors/genetics/metabolism[MESH]|Gene Expression Regulation[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit[MESH]|Intercellular Signaling Peptides and Proteins/genetics/metabolism[MESH]|Lymphokines/genetics/metabolism[MESH]|Neoplasms/*blood supply/genetics/metabolism[MESH]|Nuclear Proteins/*physiology[MESH]|Transcription Factors/genetics/*metabolism[MESH]|Vascular Endothelial Growth Factor A[MESH]|Vascular Endothelial Growth Factors[MESH] |