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Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.

Oncogene | Mar 21, 1996

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 RIS Download

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