Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1

Eduardo Salido; David J. Timson; Isabel Betancor-Fernández; Rogelio Palomino-Morales; Angel L. Pey

doi:10.20944/preprints202003.0285.v1

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preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202003.0285.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1

Eduardo Salido

David J. Timson

Isabel Betancor-Fernández

Rogelio Palomino-Morales

Angel L. Pey

Version 1 : Received: 17 March 2020 / Approved: 18 March 2020 / Online: 18 March 2020 (08:45:33 CET)

How to cite: Salido, E.; Timson, D.J.; Betancor-Fernández, I.; Palomino-Morales, R.; Pey, A.L. Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1. Preprints 2020, 2020030285. https://doi.org/10.20944/preprints202003.0285.v1 Salido, E.; Timson, D.J.; Betancor-Fernández, I.; Palomino-Morales, R.; Pey, A.L. Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1. Preprints 2020, 2020030285. https://doi.org/10.20944/preprints202003.0285.v1

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MDPI and ACS Style

Salido, E.; Timson, D.J.; Betancor-Fernández, I.; Palomino-Morales, R.; Pey, A.L. Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1. Preprints 2020, 2020030285. https://doi.org/10.20944/preprints202003.0285.v1

APA Style

Salido, E., Timson, D.J., Betancor-Fernández, I., Palomino-Morales, R., & Pey, A.L. (2020). Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1. Preprints. https://doi.org/10.20944/preprints202003.0285.v1

Chicago/Turabian Style

Salido, E., Rogelio Palomino-Morales and Angel L. Pey. 2020 "Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1" Preprints. https://doi.org/10.20944/preprints202003.0285.v1

Abstract

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 HIF-1α interaction with NQO1 inhibits its proteasomal degradation, thus suggesting that targeting the stability of NQO1 could led to destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, we review here our current knowledge on the intracellular functions and stability of NQO1, its pharmacological modulation by small ligands, and the molecular determinants of its roles as a chaperone of many different proteins including cancer-associated factors such as p53 and p73α. This knowledge is then 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.

Keywords

HIF-1α; NQO1; hypoxia; angiogenesis; cancer; protein:protein interactions; ligand binding; proteasomal degradation

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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