BRD4 as a potential target for human papillomaviruses associated cancer

J Med Virol. 2023 Dec;95(12):e29294. doi: 10.1002/jmv.29294.

Abstract

Around 99% of cervical cancer and 5%-10% of human cancer are associated with human papillomaviruses (HPV). Notably, the life-cycle of HPV begins by low-level infection of the basal cells of the stratified epithelium, where the viral genomes are replicated and passed on to the daughter proliferating basal cells. The production of new viral particles remains restricted to eventually differentiated cells. HPVs support their persistent infectious cycle by hijacking pivotal pathways and cellular processes. Bromodomain-containing protein 4 (BRD4) is one of the essential cellular factors involved in multiple stages of viral transcription and replication. In this review, we demonstrate the role of BRD4 in the multiple stages of HPV infectious cycle. Also, we provide an overview of the intense research about the cellular functions of BRD4, the mechanism of action of bromodomain and extra terminal inhibitors, and how it could lead to the development of antiviral/anticancer therapies.

Keywords: antiviral agents; cell cultures: research and analysis methods; human immunodeficiency virus: vrus classification; human papillomavirus: virus classification; oncogenesis.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bromodomain Containing Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Human Papillomavirus Viruses
  • Humans
  • Neoplasms*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Papillomaviridae / genetics
  • Papillomavirus Infections*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Virus Replication

Substances

  • Transcription Factors
  • Nuclear Proteins
  • BRD4 protein, human
  • Bromodomain Containing Proteins
  • Cell Cycle Proteins