Integration of a growth-suppressing BTB/POZ domain protein with the DP component of the E2F transcription factor.
Transcription factor E2F plays an important role in orchestrating early cell cycle progression through its ability to co-ordinate and integrate the cell cycle with the transcription apparatus. Physiological E2F arises when members of two distinct families of proteins interact as E2F-DP heterodimers, in which the E2F component mediates transcriptional activation and the physical interaction with pocket proteins, such as the tumour suppressor protein pRb. In contrast, a discrete role for the DP subunit has not been defined. We report the identification and characterization of DIP, a novel mammalian protein that can interact with the DP component of E2F. DIP was found to contain a BTB/POZ domain and shows significant identity with the Drosophila melanogaster germ cell-less gene product. In mammalian cells, DIP is distributed in a speckled pattern at the nuclear envelope region, and can direct certain DP subunits and the associated heterodimeric E2F partner into a similar pattern. DIP-dependent growth arrest is modulated by the expression of DP proteins, and mutant derivatives of DIP that are compromised in cell cycle arrest exhibit reduced binding to the DP subunit. Our study defines a new pathway of growth control that is integrated with the E2F pathway through the DP subunit of the heterodimer.
de la Luna
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S
Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK.
Allen
K E
KE
Mason
S L
SL
La Thangue
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NB
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D050684:E2F Transcription Factors; D006131:Growth Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D056465:Retinoblastoma-Binding Protein 1; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C117145:DP-interacting protein, mouse; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C471550:Gcl protein, mouse; D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; C076187:gcl protein, Drosophila