Cdk2-dependent phosphorylation of Id2 modulates activity of E2A-related transcription factors

EMBO J. 1997 Jan 15;16(2):332-42. doi: 10.1093/emboj/16.2.332.

Abstract

The helix-loop-helix (HLH) protein Id2 is thought to affect the balance between cell growth and differentiation by negatively regulating the function of basic-helix-loop-helix (bHLH) transcription factors. Id2 acts by forming heterodimers that are unable to bind to specific (E-box) DNA sequences. Here we show that this activity can be overcome by phosphorylation of a serine residue within a consensus target site for cyclin-dependent kinases (Cdks). In vitro, Id2 can be phosphorylated by either cyclin E-Cdk2 or cyclin A-Cdk2 but not by cyclin D-dependent kinases. Analogous phosphorylation occurs in serum-stimulated human diploid fibroblasts at a time in late G1 consistent with the appearance of active cyclin E-Cdk2. The phosphorylation of Id2 in these cells correlates with the restoration of a distinct E-box-dependent DNA-binding complex, suggesting that the levels of this complex are modulated by both the abundance and phosphorylation status of Id2. These data provide a link between cyclin-dependent kinases and bHLH transcription factors that may be critical for the regulation of cell proliferation and differentiation.

MeSH terms

  • 3T3 Cells
  • Adenovirus E2 Proteins / metabolism*
  • Animals
  • Binding Sites
  • CDC2-CDC28 Kinases*
  • Cell Cycle
  • Cell Division
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / metabolism
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / metabolism
  • Helix-Loop-Helix Motifs*
  • Humans
  • Mice
  • Peptide Mapping
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Resting Phase, Cell Cycle
  • S Phase
  • Transcription Factors / metabolism*

Substances

  • Adenovirus E2 Proteins
  • Cyclins
  • DNA-Binding Proteins
  • Transcription Factors
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases