Phenotypic Modulation of Cancer-Associated Antioxidant NQO1 Activity by Post-Translational Modifications and the Natural Diversity of the Human Genome.
Angel L PeyPublished in: Antioxidants (Basel, Switzerland) (2023)
Human NAD(P)H:quinone oxidoreductase 1 (hNQO1) is a multifunctional and antioxidant stress protein whose expression is controlled by the Nrf2 signaling pathway. hNQO1 dysregulation is associated with cancer and neurological disorders. Recent works have shown that its activity is also modulated by different post-translational modifications (PTMs), such as phosphorylation, acetylation and ubiquitination, and these may synergize with naturally-occurring and inactivating polymorphisms and mutations. Herein, I describe recent advances in the study of the effect of PTMs and genetic variations on the structure and function of hNQO1 and their relationship with disease development in different genetic backgrounds, as well as the physiological roles of these modifications. I pay particular attention to the long-range allosteric effects exerted by PTMs and natural variation on the multiple functions of hNQO1.
Keyphrases
- endothelial cells
- oxidative stress
- signaling pathway
- genome wide
- induced pluripotent stem cells
- small molecule
- pluripotent stem cells
- squamous cell carcinoma
- papillary thyroid
- gene expression
- binding protein
- copy number
- working memory
- health insurance
- epithelial mesenchymal transition
- dna methylation
- long non coding rna
- brain injury
- induced apoptosis
- young adults
- histone deacetylase
- childhood cancer
- protein kinase