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Chen CY, Li Y, Jia T, et al. Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides. Med Chem Res. 2020;29(4):607-616doi: 10.1007/s00044-019-02493-4.
Chen, C. Y., Li, Y., Jia, T., He, L., Hare, A. A., Silberstein, A., Gallagher, J., Martinez, T. F., Stiles, J. W., Olenyuk, B., Dervan, P. B., & Stiles, B. L. (2020). Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides. Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 29(4), 607-616. https://doi.org/10.1007/s00044-019-02493-4
Chen, Chien-Yu, et al. "Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides." Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents vol. 29,4 (2020): 607-616. doi: https://doi.org/10.1007/s00044-019-02493-4
Chen CY, Li Y, Jia T, He L, Hare AA, Silberstein A, Gallagher J, Martinez TF, Stiles JW, Olenyuk B, Dervan PB, Stiles BL. Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides. Med Chem Res. 2020 Apr;29(4):607-616. doi: 10.1007/s00044-019-02493-4. Epub 2020 Feb 26. PMID: 34552311; PMCID: PMC8455084.
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Med Chem Res. 2020 Apr;29(4):607-616. doi: 10.1007/s00044-019-02493-4. Epub 2020 Feb 26.

Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides.

Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents

Chien-Yu Chen, Yang Li, Tiezheng Jia, Lina He, Alissa A Hare, Amanda Silberstein, John Gallagher, Thomas F Martinez, Joseph W Stiles, Bogdan Olenyuk, Peter B Dervan, Bangyan L Stiles

Affiliations

  1. Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA.
  2. Present address: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
  3. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  4. Present address: SUSTECH, 1088 Xueyuan Avenue, Shenzhen, Guangdong Province 518055, P. R. China.
  5. Present address: Vanderbilt, Nashville, TN 37240, USA.
  6. Present address: Westmont College, 955 La Paz Rd, Santa Barbara, CA 93108, USA.
  7. Present address: Salk Institute, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
  8. Present address: Princeton University, Princeton, NJ 08544, USA.
  9. Present address: PRISM, 505 Coast Blvd. S., Suite 206, La Jolla, CA 92037, USA.

PMID: 34552311 PMCID: PMC8455084 DOI: 10.1007/s00044-019-02493-4

Abstract

The orphan nuclear receptors estrogen-related receptors (ERRs) bind to the estrogen-related receptor response element (ERRE) to regulate transcriptional programs in cellular metabolism and cancer cell growth. In this study, we evaluated the potential for a pyrrole-imidazole polyamide to block ERRα binding to ERREs to inhibit gene expression. We demonstrated that the ERRE-targeted polyamide 1 blocked the binding of ERRα to the consensus ERRE and reduced the transcriptional activity of ERRα in cell culture. We further showed that inhibiting ERRα transcriptional activity with polyamide 1 led to reduced mitochondrial oxygen consumption, a primary biological effect regulated by ERRα. Finally, our data demonstrated that polyamide 1 is an inhibitor for cancer cell growth.

Keywords: ERRα; Mitochondria; Pyrrole-imidazole polyamide

Conflict of interest statement

Conflict of interest The authors declare that they have no conflict of interest.

References

  1. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8912-7 - PubMed
  2. J Cell Biochem. 2019 Aug;120(8):13841-13852 - PubMed
  3. Mol Cell Biol. 1997 Sep;17(9):5400-9 - PubMed
  4. PLoS One. 2013 Jul 09;8(7):e67810 - PubMed
  5. Front Endocrinol (Lausanne). 2019 Apr 05;10:206 - PubMed
  6. J Biol Chem. 1997 Dec 12;272(50):31693-9 - PubMed
  7. Mol Cancer Res. 2017 Oct;15(10):1366-1375 - PubMed
  8. J Biol Chem. 2003 Sep 19;278(38):36027-31 - PubMed
  9. Free Radic Biol Med. 2011 Nov 1;51(9):1621-35 - PubMed
  10. Chem Biol Interact. 2009 Oct 7;181(2):236-42 - PubMed
  11. Nucleic Acids Res. 2017 Sep 19;45(16):9219-9228 - PubMed
  12. Mol Endocrinol. 2008 Oct;22(10):2215-28 - PubMed
  13. Int J Cancer. 2007 Jun 1;120(11):2325-30 - PubMed
  14. J Biol Chem. 2013 Aug 30;288(35):25007-25024 - PubMed
  15. Mitochondrion. 2011 Jul;11(4):544-52 - PubMed
  16. Cancer Commun (Lond). 2018 May 21;38(1):27 - PubMed
  17. Biochem Biophys Res Commun. 2007 Jul 6;358(3):813-8 - PubMed
  18. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6472-7 - PubMed
  19. J Biol Chem. 2004 Dec 10;279(50):52052-8 - PubMed
  20. Oncotarget. 2016 Nov 22;7(47):77071-77086 - PubMed
  21. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10418-23 - PubMed
  22. Cancer Manag Res. 2018 Dec 12;10:6887-6895 - PubMed
  23. Org Lett. 2012 Jun 1;14(11):2774-7 - PubMed
  24. Cell Metab. 2007 May;5(5):345-56 - PubMed
  25. Mol Cell Biol. 2003 Nov;23(22):7947-56 - PubMed
  26. Cancers (Basel). 2018 Nov 15;10(11): - PubMed
  27. J Biol Chem. 2017 Dec 22;292(51):21102-21116 - PubMed
  28. Acta Pharmacol Sin. 2015 Jan;36(1):71-87 - PubMed
  29. Endocr Rev. 2008 Oct;29(6):677-96 - PubMed
  30. Carcinogenesis. 2013 Oct;34(10):2253-61 - PubMed
  31. Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16768-73 - PubMed
  32. Biochem J. 2013 Sep 15;454(3):371-86 - PubMed
  33. Trends Endocrinol Metab. 2008 Oct;19(8):269-76 - PubMed
  34. ACS Omega. 2018 Mar 31;3(3):3608-3616 - PubMed
  35. Mol Cancer Ther. 2013 May;12(5):675-84 - PubMed
  36. J Clin Endocrinol Metab. 2005 Mar;90(3):1830-44 - PubMed
  37. Curr Opin Struct Biol. 2003 Jun;13(3):284-99 - PubMed
  38. Biochemistry. 2014 Jul 29;53(29):4839-46 - PubMed
  39. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12378-83 - PubMed
  40. Am J Cancer Res. 2018 May 01;8(5):778-791 - PubMed
  41. Genes Dev. 2010 Mar 15;24(6):537-42 - PubMed
  42. Mol Endocrinol. 2007 Jan;21(1):62-76 - PubMed
  43. Cell Metab. 2007 Jul;6(1):13-24 - PubMed
  44. Mol Cancer Res. 2011 Dec;9(12):1708-17 - PubMed
  45. Pediatr Res. 2005 May;57(5 Pt 2):78R-86R - PubMed
  46. Oncol Lett. 2012 Dec;4(6):1151-1157 - PubMed
  47. J Mol Cell Cardiol. 2013 Dec;65:88-97 - PubMed
  48. Mol Cell Biol. 2005 Feb;25(4):1354-66 - PubMed
  49. Mol Cell Biol. 2008 Oct;28(19):5986-95 - PubMed

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