Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II.
The product of the human oncogene ELL encodes an RNA polymerase II transcription factor that undergoes frequent translocation in acute myeloid leukemia (AML). In addition to its elongation activity, ELL contains a novel type of RNA polymerase II interaction domain that is capable of repressing polymerase activity in promoter-specific transcription. Remarkably, the ELL translocation that is found in patients with AML results in the deletion of exactly this functional domain. Here we report that the EAP30 subunit of the ELL complex has sequence homology to the Saccharomyces cerevisiae SNF8, whose genetic analysis suggests its involvement in the derepression of gene expression. Remarkably, EAP30 can interact with ELL and derepress ELL's inhibitory activity in vitro. This finding may reveal a key role for EAP30 in the pathogenesis of human leukemia.
Edward A. Doisy Department of Biochemistry, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, USA.
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Schmidt
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Miller
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Schmidt
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Shiekhattar
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Shilatifard
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D004794:Enzyme Repression; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009857:Oncogenes; D010445:Peptide Elongation Factors; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors
D004268:DNA-Binding Proteins; C090862:ELL protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D010445:Peptide Elongation Factors; D011994:Recombinant Proteins; C094045:SNF8 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II