EVI1 promotes cell proliferation by interacting with BRG1 and blocking the repression of BRG1 on E2F1 activity.
EVI1 is a complex protein required for embryogenesis and inappropriately expressed in many types of human myeloid leukemia. Earlier we showed that the forced expression of EVI1 in murine hematopoietic precursor cells leads to their abnormal differentiation and increased proliferation. In this report, we show that EVI1 physically interacts with BRG1 and its functional homolog BRM in mammalian cells. We found that the C terminus of EVI1 interacts strongly with BRG1 and that the central and C-terminal regions of BRG1 are involved in EVI1-BRG1 interaction. Using reporter gene assays, we demonstrate that EVI1 activates the E2F1 promoter in NIH3T3 cells but not in BRG1-negative SW13 cells. Ectopic expression of BRG1 is able to repress the E2F1 promoter in vector-transfected SW13 cells but not in EVI1-transfected SW13 cells. Finally, we show that EVI1 up-regulates cell proliferation in BRG1-positive 32Dcl3 cells but not in BRG1-negative SW13 cells. Taken together, these data support the hypothesis that the interaction with BRG1 is important for up-regulation of cell-growth by EVI1.
Chi
Yiqing
Y
Department of Pathology and The Cancer Center, University of Illinois, Chicago, Illinois 60607, USA.
Senyuk
Vitalyi
V
Chakraborty
Soumen
S
Nucifora
Giuseppina
G
D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000502:physiology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005434:Flow Cytometry; D017353:Gene Deletion; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D008156:Luciferases; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases