Determination of sequences responsible for the differential regulation of Myc function by delta Max and Max

Oncogene. 1995 Aug 3;11(3):553-60.

Abstract

The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally occurring truncated form of Max, delta Max, which in a rat embryo fibroblast enhances transformation by Myc and Ras. Like Max, this delta Max protein contains a b-HLH-Zip domain, except that the end of the leucine zipper is replaced by five delta Max-specific amino acid residues. Delta Max also lacks the C-terminal sequences of Max including a nuclear localisation signal. Here we have dissected the regions responsible for the specific effects of Max and delta Max in Ras-Myc cotransformation of rat embryo fibroblasts. Our results indicate that the suppressive activity of Max requires C-terminal acidic and basic regions and an intact leucine zipper. Replacement of the end of the leucine zipper with the delta Max-specific sequence is responsible for the enhancement of transformation by delta Max. Surprisingly, delta Max does not require the DNA-binding basic region for enhancement of transformation and has no effect on Myc-induced transcription activation from Myc/Max-binding site-containing promoter construct.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • Cell Compartmentation
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / physiology
  • Helix-Loop-Helix Motifs
  • In Vitro Techniques
  • Leucine Zippers
  • Macromolecular Substances
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / physiology*
  • Rats
  • Sequence Deletion
  • Structure-Activity Relationship
  • Transcription Factors / chemistry*
  • Transcription Factors / physiology

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Max protein, rat
  • Myc associated factor X
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors