AI Article Synopsis

  • EVI1 is a crucial protein for early development that is improperly expressed in various types of human leukemia, promoting abnormal cell behaviors when overexpressed.
  • The research highlights that EVI1 physically interacts with BRG1, a protein involved in regulating gene expression, and specific regions of both proteins are key for this interaction.
  • Findings suggest that EVI1 enhances cell proliferation in cells that express BRG1 while demonstrating that BRG1 can negatively affect E2F1 promoter activity, indicating their interaction is vital for EVI1's role in promoting cell growth.

Article Abstract

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.

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http://dx.doi.org/10.1074/jbc.M309645200DOI Listing

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