title: E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domains.
abstract: The E2F family of transcription factors play an important role in regulating cell cycle progression. We report here the characterization and functional properties of a new member of the human E2F family, referred to as E2F-7. E2F-7 has two separate DNA-binding domains, a feature that distinguishes E2F-7 from other mammalian E2F proteins, but resembling the organization of recently isolated E2F-like proteins from Arabidopsis. E2F-7 binds to DNA independently of a DP partner and delays cell cycle progression. Interestingly, E2F-7 modulates the transcription properties of other E2F proteins. A mutational analysis indicates that the integrity of both DNA-binding domains is required for cell cycle delay and transcriptional modulation. Biochemical results and protein modelling studies suggest that in binding to DNA interactions occur between the two DNA-binding domains, most probably as a homodimer, thereby mimicking the organization of an E2F/DP heterodimer. These structural and functional properties of E2F-7 imply a unique role in regulating cellular proliferation.
authors.affiliation: Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Logan
authors.forename: Laurent
authors.initials: L
authors.lastname: Delavaine
authors.forename: Anne
authors.initials: A
authors.lastname: Graham
authors.forename: Carmel
authors.initials: C
authors.lastname: Reilly
authors.forename: Jon
authors.initials: J
authors.lastname: Wilson
authors.forename: Thijn R
authors.initials: TR
authors.lastname: Brummelkamp
authors.forename: E Marielle
authors.initials: EM
authors.lastname: Hijmans
authors.forename: René
authors.initials: R
authors.lastname: Bernards
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D050702:E2F7 Transcription Factor; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050702:E2F7 Transcription Factor; C481054:E2F7 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D008156:Luciferases