An alternative pathway for gene regulation by Myc

EMBO J. 1997 Sep 15;16(18):5672-86. doi: 10.1093/emboj/16.18.5672.


The c-Myc protein activates transcription as part of a heteromeric complex with Max. However, Myc-transformed cells are characterized by loss of expression of several genes, suggesting that Myc may also repress gene expression. Two-hybrid cloning identifies a novel POZ domain Zn finger protein (Miz-1; Myc-interacting Zn finger protein-1) that specifically interacts with Myc, but not with Max or USF. Miz-1 binds to start sites of the adenovirus major late and cyclin D1 promoters and activates transcription from both promoters. Miz-1 has a potent growth arrest function. Binding of Myc to Miz-1 requires the helix-loop-helix domain of Myc and a short amphipathic helix located in the carboxy-terminus of Miz-1. Expression of Myc inhibits transactivation, overcomes Miz-1-induced growth arrest and renders Miz-1 insoluble in vivo. These processes depend on Myc and Miz-1 association and on the integrity of the POZ domain of Miz-1, suggesting that Myc binding activates a latent inhibitory function of this domain. Fusion of a nuclear localization signal induces efficient nuclear transport of Miz-1 and impairs the ability of Myc to overcome transcriptional activation and growth arrest by Miz-1. Our data suggest a model for how gene repression by Myc may occur in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adenoviridae / genetics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Gene Library
  • Genes, Reporter
  • HeLa Cells
  • Helix-Loop-Helix Motifs
  • Humans
  • Kruppel-Like Transcription Factors
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Transfection
  • Viral Proteins
  • Zinc Fingers


  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • MLTF protein, adenovirus
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Viral Proteins
  • ZBTB17 protein, human
  • Cyclin D1

Associated data

  • GENBANK/Y09723