DTIC ADA435415: Hypoxia Inducible Factor Prolyl Hydroxylases pdf

DTIC ADA435415: Hypoxia Inducible Factor Prolyl Hydroxylases

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In mammalian cells, molecular oxygen is a requirement for normal growth, metabolism, and survival. Tissues in which oxygen demand surpasses oxygen supply become hypoxic and cannot maintain normal function. Thus, the ability to sense oxygen levels is necessary for an organism to survive and thrive in changing environmental and physiological conditions. HIF-1 is a transcription factor complex that is essential and central to several cellular and systemic adaptations to hypoxia. For example, vascular endothelial growth factor and erythropoietin are HIF-1 target genes that are important in angiogenesis and erythropoiesis, respectively. HIF-1 consists of two subunits, alpha and beta, and control of HIF-1 function is accomplished through the hydroxylation of proline residues and an asparagine residue on the -subunit of HIF-1. Under normoxic conditions, hydroxylated HIF-1 is constantly and rapidly degraded, thus HIF-1 is inactivated. Additionally, undegraded HIF-1 is hydroxylated at an asparagine residue in the c-terminal region, which prevents it from binding to the co-transcriptional activator p300

• Creator/s: Defense Technical Information Center
• Date: 3/1/2005
• Year: 2005
• Book Topics/Themes: DTIC Archive, Dalgard, Clifton, UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD, *BRAIN, *OXYGEN, *HYPOXIA, FUNCTIONS, DETECTORS, THESES, SURVIVAL(GENERAL), CELLS(BIOLOGY), MOLECULAR PROPERTIES, ERYTHROPOIESIS, ERYTHROPOIETINS

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