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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells / metabolism
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3T3 Cells / physiology
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Animals
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Base Sequence
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Binding Sites
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Carrier Proteins*
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Cell Cycle / physiology
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Cell Cycle Proteins*
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Cloning, Molecular
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Cyclins / biosynthesis*
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Cyclins / genetics
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DNA / genetics
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DNA / isolation & purification
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DNA-Binding Proteins*
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E2F Transcription Factors
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Gene Expression Regulation, Neoplastic / physiology*
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Humans
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Mice
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Molecular Sequence Data
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Osteosarcoma / genetics
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Osteosarcoma / metabolism
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Promoter Regions, Genetic / physiology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Retinoblastoma Protein / physiology*
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors / physiology*
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Transcription, Genetic / physiology
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Tumor Cells, Cultured
Substances
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Arid4a protein, mouse
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Carrier Proteins
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Cell Cycle Proteins
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Cyclins
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DNA-Binding Proteins
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E2F Transcription Factors
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RNA, Messenger
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Retinoblastoma Protein
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors
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DNA