Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.
Journal:
Oncogene 1996 MarAuthors:
Geng Y, Eaton EN, Picón M, Roberts JM, Lundberg AS, Gifford A, Sardet C, Weinberg RA
Abstract
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 re
...[more]port 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.[less]
Mesh Headings:
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