Ras induces elevation of E2F-1 mRNA levels.
Both E2F-1 and Ras play pivotal roles in the regulation of cell proliferation, and in some biological settings, they collaborate in cell transformation. We show here that activated Ras induces an increase in E2F-1 mRNA and protein levels. This Ras-induced increase in E2F-1 levels is dependent on both MEK and PKB, and it is retinoblastoma-independent. The effect of Ras on the up-regulation of E2F-1 mRNA is at the level of mRNA stability. Our data describe a novel functional link between Ras and the retinoblastoma/E2F pathway. Furthermore, we suggest that one of the molecular mechanisms underlying the collaboration between Ras and E2F-1 involves a Ras-induced elevation of transcriptionally active E2F-1 levels.
Berkovich
E
E
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Ginsberg
D
D
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005347:Fibroblasts / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012190:Retroviridae / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; C493755:E2f1 protein, rat; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D018631:ras Proteins