Myc and its interactors take shape

Biochim Biophys Acta. 2015 May;1849(5):469-83. doi: 10.1016/j.bbagrm.2014.06.002. Epub 2014 Jun 14.


The Myc oncoprotein is a key contributor to the development of many human cancers. As such, understanding its molecular activities and biological functions has been a field of active research since its discovery more than three decades ago. Genome-wide studies have revealed Myc to be a global regulator of gene expression. The identification of its DNA-binding partner protein, Max, launched an area of extensive research into both the protein-protein interactions and protein structure of Myc. In this review, we highlight key insights with respect to Myc interactors and protein structure that contribute to the understanding of Myc's roles in transcriptional regulation and cancer. Structural analyses of Myc show many critical regions with transient structures that mediate protein interactions and biological functions. Interactors, such as Max, TRRAP, and PTEF-b, provide mechanistic insight into Myc's transcriptional activities, while others, such as ubiquitin ligases, regulate the Myc protein itself. It is appreciated that Myc possesses a large interactome, yet the functional relevance of many interactors remains unknown. Here, we discuss future research trends that embrace advances in genome-wide and proteome-wide approaches to systematically elucidate mechanisms of Myc action. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.

Keywords: Cancer; Myc; Post-translational modification; Protein structure; Protein–protein interaction; Transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Gene Expression Regulation
  • Genome, Human
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Conformation
  • Protein Interaction Maps / genetics*
  • Protein Processing, Post-Translational / genetics
  • Proteome*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism


  • Adaptor Proteins, Signal Transducing
  • MYC protein, human
  • Nuclear Proteins
  • Proteome
  • Proto-Oncogene Proteins c-myc
  • transformation-transcription domain-associated protein