NPDC-1, a regulator of neural cell proliferation and differentiation, interacts with E2F-1, reduces its binding to DNA and modulates its transcriptional activity.
We have previously identified NPDC-1, a neural factor involved in the control of proliferation and differentiation, and we have shown that the stable introduction of NPDC-1 into transformed cells down-regulates cell proliferation both by increasing the generation time and by suppressing transformed properties. The data presented here indicate that, in vitro, NPDC-1 is able to interact with the transcription factor E2F-1 and some cell cycle proteins, such as D-cyclins and cdk2. In addition, two-hybrid experiments in mammalian cells show that the interaction between NPDC-1 and E2F-1 can also occur in vivo. This interaction reduces the binding of E2F-1 to DNA and its transcriptional activity. Taken together, the data suggest that NPDC-1 could influence cell cycle progression and neural differentiation through its association with E2F-1.
Sansal
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I
Unité de Génétique Oncologique, CNRS-UMR-1599, Institut Gustave Roussy, PR-1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Dupont
E
E
Toru
D
D
Evrard
C
C
Rouget
P
P
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D017930:Genes, Reporter / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010449:Peptide Mapping; D011401:Promoter Regions, Genetic; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C484270:NPDC1 protein, human; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004247:DNA; D005982:Glutathione Transferase