Abstract
Two models have been proposed for the molecular mechanism by which the Tal1 oncogene causes T cell acute lymphoblastic leukemia (T-ALL). The activation model suggests that Tal1 as heterodimers with the E2A transcription factor activates the expression of oncogenes. The inhibition model postulates that Tal1 interferes with the tumor-suppressing function of E2A. In the Jurkat T cell line, originally derived from a patient with T-ALL, Tal1 is complexed with E2A proteins and the transcriptional activity of E2A is very low. When E2A activity was restored by expressing an E2A-Tal1 fusion protein, E-T/2, the Jurkat cells underwent growth arrest and subsequently apoptosis, thus supporting the inhibition model and suggesting that E2A loss may contribute to leukemic progression.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis*
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Basic Helix-Loop-Helix Transcription Factors
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Caspase Inhibitors
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Cell Division
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Culture Media, Serum-Free
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / genetics
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Humans
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Jurkat Cells
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Leukemia-Lymphoma, Adult T-Cell / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Recombinant Proteins / biosynthesis
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T-Cell Acute Lymphocytic Leukemia Protein 1
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Caspase Inhibitors
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Culture Media, Serum-Free
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DNA-Binding Proteins
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Growth Inhibitors
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Proto-Oncogene Proteins
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Recombinant Proteins
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T-Cell Acute Lymphocytic Leukemia Protein 1
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TCF Transcription Factors
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TCF7L1 protein, human
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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TAL1 protein, human
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TCF12 protein, human