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Differential effects of cdk2 and cdk3 on the control of pRb and E2F function during G1 exit.

The cyclin-dependent kinases cdk2 and cdk3 are required for the G1-S transition in mammalian cells. Here we show that G1 arrest induced by the corresponding dominant-negative mutants of these enzymes, cdk2dn or cdk3dn, is resistant to the action of SV40 T antigen (T). In the presence of cdk2dn, T released active E2F from negative control by pRb and its related family members (pocket proteins) but failed to induce S-phase. Therefore, among other targets, cdk2 also phosphorylates nonpocket protein substrates in promoting S-phase entry, and T does not mimic all cdk2 functions. In the presence of cdk3dn, however, T failed to induce cell cycle progression or stimulate E2F-dependent transcription activity. Dominant-negative cdk3 inhibited E2F-1, E2F-2, and, less significantly, E2F-3, but not E2F-4 transcription activity. The inhibition occurred in a pRb-independent manner and did not affect the DNA-binding capacity of the transcription factor. Cdk3 bound specifically to E2F-1/DP-1 complexes in vivo, most likely through DP-1. Thus, cdk3 function contributes to the activation of E2F-1, E2F-2, and partially E2F-3 and, thereby, participates in the process of S-phase entry.

Pubmed ID: 8846921


  • Hofmann F
  • Livingston DM


Genes & development

Publication Data

April 1, 1996

Associated Grants


Mesh Terms

  • Antigens, Viral, Tumor
  • Base Sequence
  • CDC2-CDC28 Kinases
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 3
  • Cyclin-Dependent Kinases
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F3 Transcription Factor
  • G1 Phase
  • Gene Expression Regulation
  • Genes, Reporter
  • Interphase
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • S Phase
  • Simian virus 40
  • Transcription Factor DP1
  • Transcription Factors
  • Transcription, Genetic