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Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.

Cyclin E is critical for the advance of cells through the G1 phase of their growth cycle. Transcription of the cyclin E gene is known to be cell cycle-dependent. We have shown previously that mRNA levels of cyclin E are regulated positively by mitogens and negatively by TGF-beta. Much circumstantial evidence implicates both E2F transcription factors and the retinoblastoma protein (pRB) in the control of cyclin E expression. However, the molecular basis of this control has remained unclear. We report here the cloning of the cyclin E promoter and the identification of several putative E2F binding sites within the promoter sequence. We have found that cell cycle regulation of cyclin E transcription is mediated by E2F binding sites present in the promoter. The activity of this promoter can be regulated negatively by pRB. Our results suggest the operation of a positive-feedback loop in late G1 that functions to ensure continued cyclin E expression and pRB inactivation.

Pubmed ID: 8649818

Authors

  • Geng Y
  • Eaton EN
  • Picón M
  • Roberts JM
  • Lundberg AS
  • Gifford A
  • Sardet C
  • Weinberg RA

Journal

Oncogene

Publication Data

March 21, 1996

Associated Grants

  • Agency: NCI NIH HHS, Id: R35-CA39826

Mesh Terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Binding Sites
  • Carrier Proteins
  • Cell Cycle
  • Cell Cycle Proteins
  • Cloning, Molecular
  • Cyclins
  • DNA
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Molecular Sequence Data
  • Osteosarcoma
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured