title: Prolyl hydroxylase domain enzymes and their role in cell signaling and cancer metabolism.
abstract: The prolyl hydroxylase domain (PHD) enzymes regulate the stability of the hypoxia-inducible factor (HIF) in response to oxygen availability. During oxygen limitation, the inhibition of PHD permits the stabilization of HIF, allowing the cellular adaptation to hypoxia. This adaptation is especially important for solid tumors, which are often exposed to a hypoxic environment. However, and despite their original role as the oxygen sensors of the cell, PHD are currently known to display HIF-independent and hydroxylase-independent functions in the control of different cellular pathways, including mTOR pathway, NF-kB pathway, apoptosis and cellular metabolism. In this review, we summarize the recent advances in the regulation and functions of PHD in cancer signaling and cell metabolism.
authors.affiliation: Institut Européen de Chimie et Biologie, 2 Rue Robert Escarpit, 33607 Pessac, France; INSERM U1218 Unit, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Tra Ly
authors.initials: TL
authors.lastname: Nguyen
authors.affiliation: Institut Européen de Chimie et Biologie, 2 Rue Robert Escarpit, 33607 Pessac, France; INSERM U1218 Unit, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux, France; University of Bordeaux, Bordeaux, France. Electronic address: raul.duran@inserm.fr.
authors.forename: Raúl V
authors.initials: RV
authors.lastname: Durán
mesh_terms: D000818:Animals; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
keywords: 2-Oxoglutarate; Cancer; Metabolism; PHD; mTOR