Physical and functional interaction of the proto-oncogene EVI1 and tumor suppressor gene HIC1 deregulates Bcl-xL mediated block in apoptosis.

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.
Mesh Terms:
Animals, Apoptosis, Colorectal Neoplasms, DNA-Binding Proteins, Fluorescence Resonance Energy Transfer, HCT116 Cells, Humans, Kruppel-Like Transcription Factors, Mice, Proto-Oncogenes, Transcription Factors, Transcription, Genetic, bcl-X Protein
Int. J. Biochem. Cell Biol.
Date: Aug. 01, 2014
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