Interaction between the pura and E2F-1 transcription factors

Anticancer Res. 2004 Sep-Oct;24(5A):2585-94.

Abstract

Background: Cell proliferation is regulated by E2F-1 which facilitates expression of genes involved in entry into S-phase. Release of E2F-1 from binding partners, e.g. pRb, is critical for G1/S progression. However ectopic E2F-1 overexpression activates p53 and inhibits growth. Previously, the multifunctional Pura protein was found to bind to E2F-1 and inhibit E2F-1 transcriptional activity.

Materials and methods: Pura deletion mutants were assayed for: in vitro binding to E2F-1, inhibition of E2F-1-induced promoter activation and effects on cell proliferation. Two RNA species with specific binding to E2F-1 and Pura were analyzed for their effects on E2F-1/Pura binding and cell growth.

Results: The N-terminal 72 amino acids of Pura were involved in E2F-1 binding, inhibition of promoter activation by E2F-1 and reversal of E2F-mediated growth inhibition. The RNA species disrupted Pura/E2F-1 interaction and affected cell growth.

Conclusion: E2F-1/Pura interaction has a role in the control of cell proliferation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cyclic AMP Response Element-Binding Protein / biosynthesis
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Medulloblastoma / genetics
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology
  • Mutagenesis
  • Promoter Regions, Genetic
  • RNA Probes / metabolism
  • Tetrahydrofolate Dehydrogenase / genetics
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation
  • Transfection

Substances

  • Cell Cycle Proteins
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • PURA protein, human
  • RNA Probes
  • Transcription Factors
  • Tetrahydrofolate Dehydrogenase