Abstract
The oncogene E2a-Pbx1 is formed by the t(1;19) translocation, which joins the N-terminal transactivation domain of E2a with the C-terminal homeodomain of PBX1. The goal of this work was to elucidate the mechanisms by which E2a-Pbx1 can lead to deregulated target gene expression. For reporter constructs it was shown that E2a-Pbx1 can activate transcription through homodimer elements (TGATTGAT) or through heterodimer elements with Hox proteins (e.g. TGATTAAT). We show a novel mechanism by which E2a-Pbx1 activates transcription of EF-9 using a promoter in intron 1 of the EF-9 gene, resulting in an aminoterminal truncated transcript. Our results indicate that the LDFS motif of E2a is essential for the transactivation of EF-9, but dispensable for transactivation of fibroblast growth factor 15. The E2a LDFS motif was also essential for proliferation of NIH3T3 fibroblasts but was dispensable for the E2a-Pbx1-induced differentiation arrest of myeloid progenitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors / chemistry
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Basic Helix-Loop-Helix Transcription Factors / physiology*
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Cell Differentiation
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Cell Line, Tumor
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Cell Proliferation
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DNA-Binding Proteins
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Fibroblasts / cytology
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Gene Expression Regulation, Neoplastic
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Histone Acetyltransferases / metabolism*
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Homeodomain Proteins / genetics*
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Humans
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Mice
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Molecular Sequence Data
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Myeloid Cells / cytology
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NIH 3T3 Cells
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Oncogene Proteins, Fusion / genetics*
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Peptide Elongation Factor 2
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Pre-B-Cell Leukemia Transcription Factor 1
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Proto-Oncogene Proteins
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Transcriptional Activation
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Homeodomain Proteins
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Oncogene Proteins, Fusion
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Peptide Elongation Factor 2
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Pre-B-Cell Leukemia Transcription Factor 1
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Proto-Oncogene Proteins
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TCF3 protein, human
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PBX1 protein, human
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E2A-Pbx1 fusion protein
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Histone Acetyltransferases
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KAT2A protein, human