Overexpression of the HIF Hydroxylases PHD1, PHD2, PHD3 and FIH Are Individually and Collectively Unfavorable Prognosticators for NSCLC Survival

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Overexpression of the HIF Hydroxylases PHD1, PHD2, PHD3 and FIH Are Individually and Collectively Unfavorable Prognosticators for NSCLC Survival

INTRODUCTION Hypoxia induced factors (HIFs) are at the heart of the adaptive mechanisms cancer cells must implement for survival. HIFs are regulated by four hydroxylases; Prolyl hydroxylase (PHD)-1,-2,-3 and factor inhibiting HIF (FIH). We aimed to investigate the prognostic impact of these oxygen sensors in NSCLC. METHODS Tumor tissue samples from 335 resected stages I to IIIA NSCLC patients...

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Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites.

The HIF (hypoxia-inducible factor) plays a central regulatory role in oxygen homoeostasis. HIF proteins are regulated by three Fe(II)- and α-KG (α-ketoglutarate)-dependent prolyl hydroxylase enzymes [PHD (prolyl hydroxylase domain) isoenzymes 1-3 or PHD1, PHD2 and PHD3] and one asparaginyl hydroxylase [FIH (factor inhibiting HIF)]. The prolyl hydroxylases control the abundance of HIF through ox...

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Loss of the oxygen sensor PHD3 enhances the innate immune response to abdominal sepsis.

Hypoxia and HIFs (HIF-1α and HIF-2α) modulate innate immune responses in the setting of systemic inflammatory responses and sepsis. The HIF prolyl hydroxylase enzymes PHD1, PHD2 and PHD3 regulate the mammalian adaptive response to hypoxia; however, their significance in the innate immune response has not been elucidated. We demonstrate in this study that deficiency of PHD3 (PHD3(-/-)) specifica...

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the innovation of a statistical model to estimate dependable rainfall (dr) and develop it for determination and classification of drought and wet years of iran

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Oxygen Sensing in Drosophila: Multiple Isoforms of the Prolyl Hydroxylase Fatiga Have Different Capacity to Regulate HIFα/Sima

BACKGROUND The Hypoxia Inducible Factor (HIF) mediates cellular adaptations to low oxygen. Prolyl-4-hydroxylases are oxygen sensors that hydroxylate the HIF alpha-subunit, promoting its proteasomal degradation in normoxia. Three HIF-prolyl hydroxylases, encoded by independent genes, PHD1, PHD2, and PHD3, occur in mammals. PHD2, the longest PHD isoform includes a MYND domain, whose biochemical f...

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ژورنال

عنوان ژورنال: PLoS ONE

سال: 2011

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0023847