A functionally distinct member of the DP family of E2F subunits.
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.
Milton
A
A
Laboratory of Cancer Biology, Nuffield Department of Clinical Laboratory Sciences, Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford, Oxon, UK.
Luoto
K
K
Ingram
L
L
Munro
S
S
Logan
N
N
Graham
A L
AL
Brummelkamp
T R
TR
Hijmans
E M
EM
Bernards
R
R
La Thangue
N B
NB
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
D002352:Carrier Proteins; D050684:E2F Transcription Factors; D021122:Protein Subunits; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1