title: Physical and functional interaction of the proto-oncogene EVI1 and tumor suppressor gene HIC1 deregulates Bcl-xL mediated block in apoptosis.
abstract: 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.
authors.affiliation: Institute of Life Sciences, Department of Gene Function and Regulation, Nalco Square, Bhubaneswar, Orissa 751023, India.
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Pradhan
authors.affiliation: Institute of Life Sciences, Department of Gene Function and Regulation, Nalco Square, Bhubaneswar, Orissa 751023, India.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Halder
authors.affiliation: Institute of Life Sciences, Department of Gene Function and Regulation, Nalco Square, Bhubaneswar, Orissa 751023, India. Electronic address: soumen_ils@yahoo.co.in.
authors.forename: Soumen
authors.initials: S
authors.lastname: Chakraborty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D045325:HCT116 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; C000715470:MAS1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D051020:bcl-X Protein
keywords: Apoptosis; Bcl-xL; EVI1; FRET; HIC1