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Publications

Journal Article Review Ppublish 12 citations

PubMed: 38100543 DOI: 10.1080/21541264.2023.2294623

Transcription factors in the development and treatment of immune disorders.

Transcription 16(1):118-140

Authors: Samantha D Patalano, Paula Fuxman Bass, Juan I Fuxman Bass

Affiliations

  • Biology Department, Boston University, Boston, MA, USA. Molecular Biology, Cellular Biology and Biochemistry Program, Boston University, Boston, MA, USA.
  • Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
  • Biology Department, Boston University, Boston, MA, USA.
  • Molecular Biology, Cellular Biology and Biochemistry Program, Boston University, Boston, MA, USA.
  • Bioinformatics Program, Boston University, Boston, MA, USA.

Abstract

Immune function is highly controlled at the transcriptional level by the binding of transcription factors (TFs) to promoter and enhancer elements. Several TF families play major roles in immune gene expression, including NF-κB, STAT, IRF, AP-1, NRs, and NFAT, which trigger anti-pathogen responses, promote cell differentiation, and maintain immune system homeostasis. Aberrant expression, activation, or sequence of isoforms and variants of these TFs can result in autoimmune and inflammatory diseases as well as hematological and solid tumor cancers. For this reason, TFs have become attractive drug targets, even though most were previously deemed "undruggable" due to their lack of small molecule binding pockets and the presence of intrinsically disordered regions. However, several aspects of TF structure and function can be targeted for therapeutic intervention, such as ligand-binding domains, protein-protein interactions between TFs and with cofactors, TF-DNA binding, TF stability, upstream signaling pathways, and TF expression. In this review, we provide an overview of each of the important TF families, how they function in immunity, and some related diseases they are involved in. Additionally, we discuss the ways of targeting TFs with drugs along with recent research developments in these areas and their clinical applications, followed by the advantages and disadvantages of targeting TFs for the treatment of immune disorders.

MeSH

Pharmaceutical Preparations, Transcription Factors, Neoplasms, Immune System Diseases, Therapeutics, Enhancer Elements, Genetic

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