Ecotropic viral integration site 1 was originally identified as a retroviral integration site in murine leukemias. Several studies have established ecotropic viral integration site 1 as both a transcription factor and an interacting partner that presumably regulates gene expression. Using coimmunoprecipitation and fluorescence resonance energy transfer analysis, we found that the N-terminal domain of hypermethylated in cancer 1 interacts with the proximal set of zinc fingers of ecotropic viral integration site 1. This interaction not only abolishes the DNA binding activity of ecotropic viral integration site 1 but also disrupts the transcriptional activity of an anti-apoptotic gene promoter selectively targeted by ecotropic viral integration site 1. By using flow cytometry and western blotting, here we show that hypermethylated in cancer 1 can deregulate ecotropic viral integration site 1-mediated blockage of apoptosis. We hypothesize that therapeutic upregulation of hypermethylated in cancer 1 may provide an important means of targeting ecotropic viral integration site 1-positive cancers.
Keywords: Apoptosis; Bcl-xL; EVI1; FRET; HIC1.
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