Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factors 1 alpha

Article Abstract:

Tumor angiogenesis and its regulation by p53-induced degradation of hypoxia-inducible factors 1 alpha are discussed. It has been shown that homozygous deletion of the p53 tumor suppressor gene using homologous recombination in a human cancer cell line promotes neovascularization and growth of tumor xenografts in nude mice. That p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1 alpha subunit of hypoxia inducible factor 1 (HIF-1). HIF-1 is a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis responding to insufficient oxygen. Amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.

Genetic aspects, Genetic regulation, Genetic transcription, Transcription (Genetics), Cellular control mechanisms, Cell regulation, Vascular endothelial growth factor, Tumor suppressor genes

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Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invation and angiogenesis

Article Abstract:

A novel functional relationship has been shown to exist in the control of tumor-associated tissue remodeling among the multifunctional cytokine TGF-beta, the hyaluronan receptor CD44, and the matrix metalloproteinase-9 (MMP-9). CD44 makes available a cell surface docking receptor for proteolytically active MMP-9 a. Localization of MMP-9 to the cell surface is necessary for ability to promote tumor invasion and angiogenesis. MMP-9 and MMP-2 both proteolytically cleave latent TGF-beta, giving a novel, potentially important mechanism for TGF-beta activation. Localization of MMP-9 to the surface of normal keratinocytes is CD44-dependent and can activate latent TGF-beta.

Cellular signal transduction, Cell membranes, Cell receptors, Plasma membranes, Cell adhesion, Cell migration, Hyaluronic acid, Metalloenzymes, Metalloproteins

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HIF-1 and human disease: one highly involved factor

Article Abstract:

Hypoxia-inducible factor 1 (HIF-1), human disease, and one highly involved factor are discussed in this review article. Topics include ischemic cardiovascular disorders, preeclampsia and intrauterine growth retardation, and pulmonary hypertension.

Statistical Data Included, Cardiovascular diseases, Preeclampsia, Embryology, Animal embryology, Messenger RNA, Ischemia, Pulmonary hypertension

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