Differential cell cycle effects induced by E2F1 mutants.
Expression of two types of transactivation-defective E2F1 mutants in human Rb-/- tumor cells led to an increase in the proportion of cells in the G1 phase of the cell cycle as determined by FACS analysis. Experiments revealed two different mechanisms of action. One mutant type induced a G1 arrest after the restriction point, with cells phenotypically at a cell cycle stage later than G1. The action of this mutant was, at least in part, dependent on specific DNA binding and was over-ridden by co-expression of its wild-type counterpart. The other mutant type, which is defective in DNA binding, slowed the G1 progression and restored a checkpoint for cell cycle withdrawal. The G1 phase withdrawal of these tumor cells allowed the initiation of skeletal muscle cell differentiation. Thus, E2F1 appears to have two different functions before and after the cell cycle restriction point. This report also may provide a basis for a gene therapy approach for certain human cancers.
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Biogen Inc., Cambridge, Massachusetts 02142, USA.
Barsoum
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D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology; D014410:Tumor Stem Cell Assay
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors