Abstract
Cyclin A is involved in the control of S phase and mitosis in mammalian cells. Expression of the cyclin A gene in nontransformed cells is characterized by repression of its promoter during the G1 phase of the cell cycle and its induction at S-phase entry. We show that this mode of regulation is mediated by the transcription factor E2F, which binds to a specific site in the cyclin A promoter. It differs from the prototype E2F site in nucleotide sequence and protein binding; it is bound by E2F complexes containing cyclin E and p107 but not pRB. Ectopic expression of cyclin D1 triggers premature activation of the cyclin A promoter by E2F, and this effect is blocked by the tumor suppressor protein p16INK4.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Base Sequence
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Carrier Proteins / physiology
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Cell Cycle Proteins*
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Cell Cycle*
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Cyclin D1
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinases / physiology
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Cyclins / genetics*
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Cyclins / physiology*
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DNA-Binding Proteins / metabolism
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E2F Transcription Factors
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Gene Expression
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Mice
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Molecular Sequence Data
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Oligodeoxyribonucleotides / chemistry
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Oncogene Proteins / physiology*
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Promoter Regions, Genetic*
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Proto-Oncogene Proteins*
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RNA, Messenger / genetics
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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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Cyclin-Dependent Kinase Inhibitor p16
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Cyclins
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DNA-Binding Proteins
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E2F Transcription Factors
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Oligodeoxyribonucleotides
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Oncogene Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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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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Cyclin D1
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Cdk4 protein, mouse
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases