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

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, Animals, Binding Sites, CDC2-CDC28 Kinases, Cell Cycle, Cell Division, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases, Cyclins, DNA-Binding Proteins, Fibroblasts, G0 Phase, Helix-Loop-Helix Motifs, Humans, Mice, Peptide Mapping, Phosphorylation, Protein-Serine-Threonine Kinases, S Phase, Transcription Factors
EMBO J.
Date: Jan. 15, 1997
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