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PMID:12234932

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Citation

Stevaux, O, Dimova, D, Frolov, MV, Taylor-Harding, B, Morris, E and Dyson, N (2002) Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2. EMBO J. 21:4927-37

Abstract

RBF1, a Drosophila pRB family homolog, is required for cell cycle arrest and the regulation of E2F-dependent transcription. Here, we describe the properties of RBF2, a second family member. RBF2 represses E2F transcription and is present at E2F-regulated promoters. Analysis of in vivo protein complexes reveals that RBF1 and RBF2 interact with different subsets of E2F proteins. dE2F1, a potent transcriptional activator, is regulated specifically by RBF1. In contrast, RBF2 binds exclusively to dE2F2, a form of E2F that functions as a transcriptional repressor. We find that RBF2-mediated repression requires dE2F2. More over, RBF2 and dE2F2 act synergistically to antagonize dE2F1-mediated activation, and they co-operate to block S phase progression in transgenic animals. The network of interactions between RBF1 or RBF2 and dE2F1 or dE2F2 reveals how the activities of these proteins are integrated. These results suggest that there is a remarkable degree of symmetry in the arrangement of E2F and RB family members in mammalian cells and in DROSOPHILA.

Links

PubMed PMC126297

Keywords

Amino Acid Sequence; Animals; Cell Cycle/physiology; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; DNA-Binding Proteins; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/embryology; Drosophila melanogaster/metabolism; E2F Transcription Factors; E2F2 Transcription Factor; Female; Male; Mice; Molecular Sequence Data; Nuclear Proteins/chemistry; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Organisms, Genetically Modified; Phylogeny; Protein Binding; Repressor Proteins/chemistry; Repressor Proteins/genetics; Repressor Proteins/metabolism; Sequence Alignment; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:E2F2

part_of

GO:0035189: Rb-E2F complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:E2F2

involved_in

GO:2000134: negative regulation of G1/S transition of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:E2F2

contributes_to

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0038390

F

Seeded From UniProt

complete

DROME:E2F2

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0038390

F

Seeded From UniProt

complete

DROME:E2F2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q24472

F

Seeded From UniProt

complete

DROME:E2F2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NIS1

F

Seeded From UniProt

complete

DROME:TFDP

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0038390

F

Seeded From UniProt

complete

DROME:TFDP

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0015799

F

Seeded From UniProt

complete

DROME:RBF

part_of

GO:0035189: Rb-E2F complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:RBF

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RBF

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0024371

F

Seeded From UniProt

complete

DROME:RBF

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011763

F

Seeded From UniProt

complete

DROME:RBF

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011766

F

Seeded From UniProt

complete

DROME:RBF

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O77051

F

Seeded From UniProt

complete

DROME:E2F1

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:E2F1

part_of

GO:0035189: Rb-E2F complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:E2F1

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0015799

F

Seeded From UniProt

complete

DROME:Q9NIS1

part_of

GO:0035189: Rb-E2F complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9NIS1

involved_in

GO:2000134: negative regulation of G1/S transition of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9NIS1

contributes_to

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0024371

F

Seeded From UniProt

complete

DROME:Q9NIS1

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011763

F

Seeded From UniProt

complete

DROME:Q9NIS1

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0024371

F

Seeded From UniProt

complete

DROME:Q9NIS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O77051

F

Seeded From UniProt

complete

DROME:Q9VF04

part_of

GO:0035189: Rb-E2F complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9VF04

involved_in

GO:2000134: negative regulation of G1/S transition of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VF04

contributes_to

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0024371

F

Seeded From UniProt

complete

DROME:Q9VF04

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011763

F

Seeded From UniProt

complete

DROME:Q9VF04

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0024371

F

Seeded From UniProt

complete


See also

References

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