Isoform-Directed Control of c-Myc Functions: Understanding the Balance from Proliferation to Growth Arrest

Int J Mol Sci. 2023 Dec 15;24(24):17524. doi: 10.3390/ijms242417524.

Abstract

The transcription factor c-Myc, a key regulator of cellular processes, has long been associated with roles in cell proliferation and apoptosis. This review analyses the multiple functions of c-Myc by examining the different c-Myc isoforms in detail. The impact of different c-Myc isoforms, in particular p64 and p67, on fundamental biological processes remains controversial. It is necessary to investigate the different isoforms in the context of proto-oncogenesis. The current knowledge base suggests that neoplastic lesions may possess the means for self-destruction via increased c-Myc activity. This review presents the most relevant information on the c-Myc locus and focuses on a number of isoforms, including p64 and p67. This compilation provides a basis for the development of therapeutic approaches that target the potent growth arresting and pro-apoptotic functions of c-Myc. This information can then be used to develop targeted interventions against specific isoforms with the aim of shifting the oncogenic effects of c-Myc from pro-proliferative to pro-apoptotic. The research summarised in this review can deepen our understanding of how c-Myc activity contributes to different cellular responses, which will be crucial in developing effective therapeutic strategies; for example, isoform-specific approaches may allow for precise modulation of c-Myc function.

Keywords: MycHex1; c-Myc S; c-Myc locus structure; mrtl; p64 isoform; p67 isoform.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Protein Isoforms / genetics
  • Proto-Oncogene Proteins c-myc* / genetics
  • RNA, Messenger

Substances

  • Protein Isoforms
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger