151055 20251017144633.0 doi 10.3390/jpm12050747 sideral 129152 ART-2022-129152 eng Salido, Eduardo Targeting HIF-1a Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1 2022 Access copy available to the general public Unrestricted HIF-1a is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1a inhibition represents an interesting target for anti-cancer therapy. It was recently shown that the HIF-1a interaction with NQO1 inhibits proteasomal degradation of the former, thus suggesting that targeting the stability and/or function of NQO1 could lead to the destabilization of HIF-1a as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1a are beginning to be unraveled, in this review we discuss: (1) Structure–function relationships of HIF-1a; (2) our current knowledge on the intracellular functions and stability of NQO1; (3) the pharmacological modulation of NQO1 by small ligands regarding function and stability; (4) the potential effects of genetic variability of NQO1 in HIF-1a levels and function; (5) the molecular determinants of NQO1 as a chaperone of many different proteins including cancer-associated factors such as HIF-1a, p53 and p73a. This knowledge is then further discussed in the context of potentially targeting the intracellular stability of HIF-1a by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies, always considering that the substantial genetic variability in NQO1 would likely result in different phenotypic responses among individuals. info:eu-repo/grantAgreement/ES/AEI/PID2019-110900GB-I00 info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 3.4 2022 MEDICINE, GENERAL & INTERNAL 67 / 169 = 0.396 2022 Q2 T2 HEALTH CARE SCIENCES & SERVICES 42 / 107 = 0.393 2022 Q2 T2 0.665 2022 Medicine (miscellaneous) 2022 Q2 2.6 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Timson, David J. Betancor-Fernández, Isabel Palomino-Morales, Rogelio Anoz-Carbonell, Ernesto (orcid)0000-0002-6649-9153 Pacheco-García, Juan Luis Medina, Milagros Universidad de Zaragoza (orcid)0000-0001-8743-0182 Pey, Ángel L. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12, 5 (2022), [28 pp.] J. pers. med. Journal of Personalized Medicine 2075-4426 3788439 http://zaguan.unizar.es/record/151055/files/texto_completo.pdf Versión publicada 2790685 http://zaguan.unizar.es/record/151055/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:151055 articulos driver 2025-10-17-14:27:35 ARTICLE