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BRD4 as a Therapeutic Target in Pulmonary Diseases. | LitMetric

BRD4 as a Therapeutic Target in Pulmonary Diseases.

Int J Mol Sci

Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.

Published: August 2023

AI Article Synopsis

  • BET proteins are key regulators of gene transcription through their interaction with acetylated histones, influencing various cellular functions like cell growth, immune responses, and inflammation.* -
  • These proteins are implicated in several lung diseases, including asthma and COPD, making them a target for new treatments; researchers are exploring small molecule inhibitors that can modulate their activity.* -
  • The review highlights BRD4's unique role and histone acetyltransferase activity in lung diseases, emphasizing the potential of BET inhibitors in preclinical models to alter disease progression.*

Article Abstract

Bromodomain and extra-terminal domain (BET) proteins are epigenetic modulators that regulate gene transcription through interacting with acetylated lysine residues of histone proteins. BET proteins have multiple roles in regulating key cellular functions such as cell proliferation, differentiation, inflammation, oxidative and redox balance, and immune responses. As a result, BET proteins have been found to be actively involved in a broad range of human lung diseases including acute lung inflammation, asthma, pulmonary arterial hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). Due to the identification of specific small molecular inhibitors of BET proteins, targeting BET in these lung diseases has become an area of increasing interest. Emerging evidence has demonstrated the beneficial effects of BET inhibitors in preclinical models of various human lung diseases. This is, in general, largely related to the ability of BET proteins to bind to promoters of genes that are critical for inflammation, differentiation, and beyond. By modulating these critical genes, BET proteins are integrated into the pathogenesis of disease progression. The intrinsic histone acetyltransferase activity of bromodomain-containing protein 4 (BRD4) is of particular interest, seems to act independently of its bromodomain binding activity, and has implication in some contexts. In this review, we provide a brief overview of the research on BET proteins with a focus on BRD4 in several major human lung diseases, the underlying molecular mechanisms, as well as findings of targeting BET proteins using pharmaceutical inhibitors in different lung diseases preclinically.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487829PMC
http://dx.doi.org/10.3390/ijms241713231DOI Listing

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