Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1 : Implications of Genetic Diversity of NQO1
HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that the HIF-1α 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-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, in this review we discuss: (1) Structure-function relationships of HIF-1α; (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-1α levels and function; (5) the molecular determinants of NQO1 as a chaperone of many different proteins including cancer-associated factors such as HIF-1α, p53 and p73α. This knowledge is then further discussed in the context of potentially targeting the intracellular stability of HIF-1α 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Journal of personalized medicine - 12(2022), 5 vom: 05. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Salido, Eduardo [VerfasserIn] |
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| Links: |
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| Themen: |
Angiogenesis |
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| Anmerkungen: |
Date Revised 16.07.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/jpm12050747 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that the HIF-1α 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-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, in this review we discuss: (1) Structure-function relationships of HIF-1α; (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-1α levels and function; (5) the molecular determinants of NQO1 as a chaperone of many different proteins including cancer-associated factors such as HIF-1α, p53 and p73α. This knowledge is then further discussed in the context of potentially targeting the intracellular stability of HIF-1α 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a angiogenesis | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a genetic variability | |
| 650 | 4 | |a hypoxia | |
| 650 | 4 | |a ligand binding | |
| 650 | 4 | |a proteasomal degradation | |
| 650 | 4 | |a protein: protein interactions | |
| 700 | 1 | |a Timson, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Betancor-Fernández, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Palomino-Morales, Rogelio |e verfasserin |4 aut | |
| 700 | 1 | |a Anoz-Carbonell, Ernesto |e verfasserin |4 aut | |
| 700 | 1 | |a Pacheco-García, Juan Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Medina, Milagros |e verfasserin |4 aut | |
| 700 | 1 | |a Pey, Angel L |e verfasserin |4 aut | |
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