Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions

Cheng, X. & Smith, J. C. Biological membrane organization and cellular signaling. Chem. Rev. 119, 5849–5880 (2019).

CAS  PubMed  Google Scholar 

Ammendolia, D. A., Bement, W. M. & Brumell, J. H. Plasma membrane integrity: implications for health and disease. BMC Biol. 19, 71 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Wang, Z. Regulation of cell cycle progression by growth factor-induced cell signaling. Cells. 10, 3327 (2021).

Bartlett, C. S., Jeansson, M. & Quaggin, S. E. Vascular growth factors and glomerular disease. Annu Rev. Physiol. 78, 437–461 (2016).

CAS  PubMed  PubMed Central  Google Scholar 

Brown, G. S., Jang, J. & Li, D. Growth factors and their roles in cardiac development and regeneration: a narrative review. Pediatr. Med. 6, (2022).

Shindo, S. et al. Phosphorylation of nuclear receptors: Novelty and therapeutic implications. Pharmacol. Ther. 248, 108477 (2023).

CAS  PubMed  Google Scholar 

Fernandez, E. J. Allosteric pathways in nuclear receptors - Potential targets for drug design. Pharmacol. Ther. 183, 152–159 (2018).

CAS  PubMed  Google Scholar 

De Bosscher, K. et al. Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation. Nat. Rev. Endocrinol. 16, 363–377 (2020).

PubMed  Google Scholar 

Pavek, P. Pregnane X receptor (PXR)-mediated gene repression and cross-talk of PXR with other nuclear receptors via coactivator interactions. Front. Pharmacol. 7, 456 (2016).

PubMed  PubMed Central  Google Scholar 

Poreba, E. & Durzynska, J. Nuclear localization and actions of the insulin-like growth factor 1 (IGF-1) system components: Transcriptional regulation and DNA damage response. Mutat. Res. Rev. Mutat. Res. 784, 108307 (2020).

CAS  PubMed  Google Scholar 

Porter, B. A., Ortiz, M. A., Bratslavsky, G. & Kotula, L. Structure and Function of the Nuclear Receptor Superfamily and Current Targeted Therapies of Prostate Cancer. Cancers (Basel). 11, (2019).

Butt, T. R. & Walfish, P. G. Human nuclear receptor heterodimers: opportunities for detecting targets of transcriptional regulation using yeast. Gene Expr. 5, 255–268 (1996).

CAS  PubMed  Google Scholar 

Penvose, A. et al. Comprehensive study of nuclear receptor DNA binding provides a revised framework for understanding receptor specificity. Nat. Commun. 10, 2514 (2019).

PubMed  PubMed Central  Google Scholar 

Zhang, D. & Heaney, A. P. Nuclear receptors as regulators of pituitary corticotroph pro-opiomelanocortin transcription. Cells 9, 900 (2020).

CAS  PubMed  PubMed Central  Google Scholar 

Wilkenfeld, S. R., Lin, C. & Frigo, D. E. Communication between genomic and non-genomic signaling events coordinate steroid hormone actions. Steroids 133, 2–7 (2018).

CAS  PubMed  Google Scholar 

Alegre-Martí, A. et al. A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance. Sci. Adv. 9, eade2175 (2023).

PubMed  PubMed Central  Google Scholar 

Saito, K. & Cui, H. Estrogen receptor alpha splice variants, post-translational modifications, and their physiological functions. Cells. 12, (2023).

Malbeteau, L. et al. HoW Protein Methylation Regulates Steroid Receptor Function. Endocr. Rev. 43, 160–197 (2022).

PubMed  Google Scholar 

Brunmeir, R. & Xu, F. Functional regulation of ppars through post-translational modifications. Int. J. Mol. Sci. 19, (2018).

Fu, T. et al. FXR regulates intestinal cancer stem cell proliferation. Cell 176, 1098–1112.e1018 (2019).

CAS  PubMed  PubMed Central  Google Scholar 

Ma, H. et al. The nuclear receptor THRB facilitates differentiation of human PSCs into more mature hepatocytes. Cell Stem Cell 29, 795–809.e711 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Tschuck, J. et al. Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis. Nat. Commun. 14, 6908 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Lambrecht, R. et al. Liver receptor homolog-1 (NR5A2) orchestrates hepatic inflammation and TNF-induced cell death. Cell Rep. 42, 113513 (2023).

CAS  PubMed  Google Scholar 

Meinsohn, M. C., Smith, O. E., Bertolin, K. & Murphy, B. D. The orphan nuclear receptors steroidogenic factor-1 and liver receptor homolog-1: StrUcture, Regulation, And Essential Roles In Mammalian Reproduction. Physiol. Rev. 99, 1249–1279 (2019).

CAS  PubMed  Google Scholar 

Font-Díaz, J. et al. Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development. Semin. Cancer Biol. 73, 58–75 (2021).

PubMed  Google Scholar 

Zhao, L., Hu, H., Gustafsson, J. & Zhou, S. Nuclear receptors in cancer inflammation and immunity. Trends Immunol. 41, 172–185 (2020).

CAS  PubMed  Google Scholar 

Yang, P. B. et al. Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression. Proc. Natl. Acad. Sci. USA 117, 27412–27422 (2020).

CAS  PubMed  PubMed Central  Google Scholar 

Wu, Q. et al. Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis. J. Clin. Invest. 131, (2021).

Jiang, J. et al. Systematic pan-cancer characterization of nuclear receptors identifies potential cancer biomarkers and therapeutic targets. Cancer Res 82, 46–59 (2022).

CAS  PubMed  Google Scholar 

Doyon, G. & Bruemmer, D. Vascular smooth muscle cell dysfunction in diabetes: nuclear receptors channel to relaxation. Clin. Sci. (Lond.) 130, 1837–1839 (2016).

CAS  PubMed  Google Scholar 

Pritchard, K. I. et al. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group. J. Clin. Oncol. 15, 2302–2311 (1997).

CAS  PubMed  Google Scholar 

Kenda, M. & Sollner Dolenc, M. Computational study of drugs targeting nuclear receptors. Molecules 25, 1616 (2020).

CAS  PubMed  PubMed Central  Google Scholar 

van de Wiel, S. M. W., Bijsmans, I. T. G. W., van Mil, S. W. C. & van de Graaf, S. F. J. Identification of FDA-approved drugs targeting the Farnesoid X Receptor. Sci. Rep. 9, 2193 (2019).

PubMed  PubMed Central  Google Scholar 

Kim, H. et al. Tamoxifen response at single-cell resolution in estrogen receptor-positive primary human breast tumors. Clin. Cancer Res. 29, 4894–4907 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Zhang, N. et al. Identifying actionable druggable targets for breast cancer: Mendelian randomization and population-based analyses. EBioMedicine 98, 104859 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Freedland, S. J. et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N. Engl. J. Med. 389, 1453–1465 (2023).

CAS  PubMed  Google Scholar 

Armstrong, A. J. et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J. Clin. Oncol. 40, 1616–1622 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Lazar, M. A. Reversing the curse on PPARγ. J. Clin. Invest. 128, 2202–2204 (2018).

PubMed  PubMed Central  Google Scholar 

Dormandy, J. A. et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366, 1279–1289 (2005).

CAS  PubMed  Google Scholar 

Huss, J. M. & Kelly, D. P. Nuclear receptor signaling and cardiac energetics. Circ. Res. 95, 568–578 (2004).

CAS  PubMed  Google Scholar 

Vega, R. B. & Kelly, D. P. Cardiac nuclear receptors: architects of mitochondrial structure and function. J. Clin. Invest. 127, 1155–1164 (2017).

PubMed  PubMed Central  Google Scholar 

Vance, M. L. Growth-hormone-releasing hormone. Clin. Chem. 36, 415–420 (1990).

CAS  PubMed  Google Scholar 

Xu, H. E. Family reunion of nuclear hormone receptors: Structures, diseases, and drug discovery. Acta Pharm. Sin. 36, 1–2 (2015).

Comments (0)

No login
gif