Identification of casein kinase II phosphorylation sites in Max: effects on DNA-binding kinetics of Max homo- and Myc/Max heterodimers

Oncogene. 1993 Dec;8(12):3211-20.

Abstract

Myc proteins have been implicated in the regulation of cell growth and differentiation. The identification of Max, a basic region/helix-loop-helix/leucine zipper protein, as a partner for Myc has provided insights into Myc's molecular function as a transcription factor. Recent evidence indicates that the relative abundance of Myc and Max is important to determine the level of specific gene transcription. In this report we have identified two major in vivo phosphorylation sites in Max (Ser-2 and -11) which can be modified in vitro by casein kinase II (CKII). Phosphorylation of these sites modulates DNA-binding by increasing both the on- and off-rates of Max homo- as well as Myc/Max heterodimers. In addition, our data indicate that the steady state binding of the shorter version of Max (p21) to DNA was similar yet its rate of dissociation faster than that of longer version of Max (p22). These data argue that different Max complexes have different kinetic properties and that these can be modified by CKII phosphorylation. We propose this as an important biological mechanism by which different dimeric complexes can exchange with varying efficiencies on DNA, thereby responding to changes in cell growth conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / pathology
  • Casein Kinase II
  • Cell Division / physiology
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Molecular Sequence Data
  • Peptide Mapping
  • Phosphorylation
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Proto-Oncogene Proteins c-myc / physiology
  • Serine / analysis
  • Serine / physiology
  • Transcription Factors*
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • MAX protein, human
  • Myc associated factor X
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Serine
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases