Proteolytic control of the oncoprotein transcription factor Myc

Adv Cancer Res. 2011;110:77-106. doi: 10.1016/B978-0-12-386469-7.00004-9.

Abstract

The c-Myc oncogene encodes a multifunctional transcription factor that directs the expression of genes required for cell growth and proliferation. Consistent with its potent growth-promoting properties, cells have evolved numerous mechanisms that limit the expression and activity of Myc. One of the most prominent of these mechanisms is proteolysis, which destroys Myc within minutes of its synthesis. The rapid and controlled destruction of Myc keeps its levels low and precisely tied to processes that regulate Myc production. In this review, we discuss how Myc protein stability is regulated and the influence of Myc proteolysis on its function. We describe what is known about how Myc is destroyed by ubiquitin (Ub)-mediated proteolysis, attempt to rationalize the role of different Ub-protein ligases and deubiquitylating enzymes (dUbs) in the regulation of Myc stability, and detail how these processes go awry in cancer. Finally, we discuss how our understanding of Myc regulation by the ubiquitin-proteasome system (UPS) can expose strategies for therapeutic intervention in human malignancies.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Proto-Oncogene Proteins c-myc
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex