title: A functionally distinct member of the DP family of E2F subunits.
abstract: E2F transcription factors regulate genes involved in cell-cycle progression. In mammalian cells, physiological E2F exists as an E2F/DP heterodimer. Currently, eight E2F and two DP subunits have been characterized. We report here the characterization of a new member of the DP family, DP-4. While DP-4 exhibits certain similarities with members of the DP family, it also possesses a number of significant differences. Thus, DP-4 forms a heterodimer with E2F subunits, binds to the E2F site and associates with pocket proteins including pRb. In contrast to DP-1, however, DP-4/E2F-1 complexes exhibit reduced DNA binding activity. Furthermore, DP-4 interferes with E2F-1-dependent transcription and delays cell-cycle progression. These results highlight an emerging complexity in the DP family of E2F subunits, and suggest that DP-4 may endow E2F heterodimers with distinct transcription properties.
authors.affiliation: Laboratory of Cancer Biology, Nuffield Department of Clinical Laboratory Sciences, Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford, Oxon, UK.
authors.forename: A
authors.initials: A
authors.lastname: Milton
authors.forename: K
authors.initials: K
authors.lastname: Luoto
authors.forename: L
authors.initials: L
authors.lastname: Ingram
authors.forename: S
authors.initials: S
authors.lastname: Munro
authors.forename: N
authors.initials: N
authors.lastname: Logan
authors.forename: A L
authors.initials: AL
authors.lastname: Graham
authors.forename: T R
authors.initials: TR
authors.lastname: Brummelkamp
authors.forename: E M
authors.initials: EM
authors.lastname: Hijmans
authors.forename: R
authors.initials: R
authors.lastname: Bernards
authors.forename: N B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D003001:Cloning, Molecular; D019281:Dimerization; D050684:E2F Transcription Factors / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D012516:Osteosarcoma / Q000378:metabolism*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D050684:E2F Transcription Factors; D021122:Protein Subunits; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1