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The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
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Correction: de Melo et al. SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome. <i>Viruses</i> 2025, <i>17</i>, 619.

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Modulation of nuclear receptor function: Targeting the protein-DNA interface.

Helder Veras Ribeiro Filho1, Izabella Luisa Tambones1, Marieli Mariano Gonçalves Dias2

  • 1Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, 13083-970, Brazil; Graduate Program in Biosciences and Technology of Bioactive Products, Institute of Biology, State University of Campinas (Unicamp), Campinas, 13083-970, Brazil.

Molecular and Cellular Endocrinology
|February 1, 2019
PubMed
Summary

New strategies target nuclear receptors (NRs) beyond their ligand binding domain (LBD) to overcome drug resistance in cancers like breast and prostate cancer.

Keywords:
DNA binding domainDNA response elementsNRs alternative binding sitesNuclear receptors modulationPolyamides

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Area of Science:

  • Molecular Biology
  • Pharmacology
  • Cancer Research

Background:

  • Nuclear receptors (NRs) are critical transcription factors regulating biological processes.
  • Conventional NR modulation targets the ligand binding domain (LBD), but faces resistance in severe diseases like breast and prostate cancer.

Purpose of the Study:

  • To explore alternative strategies for modulating NR activity by inhibiting NR-DNA interactions.
  • To present challenges and perspectives for developing inhibitors targeting the DNA binding domain (DBD) or NR DNA-binding sites.

Main Methods:

  • Review of existing literature on NR modulation.
  • Analysis of strategies targeting NR DNA binding domain (DBD).
  • Examination of approaches targeting DNA sites recognized by NRs.

Main Results:

  • Discusses two distinct approaches for alternative NR modulation: targeting the DBD and targeting DNA recognition sites.
  • Highlights challenges and opportunities for developing specific inhibitors for these novel targets.

Conclusions:

  • Alternative NR modulation strategies offer promise for overcoming drug resistance in cancer.
  • Targeting NR-DBD or NR-DNA interactions represents a new frontier in NR-based therapeutics.