Abstract
TR3, an immediate-early response gene and an orphan member of the steroid-thyroid hormone-retinoid receptor superfamily of transcription factors, regulates apoptosis through an unknown mechanism. In response to apoptotic stimuli, TR3 translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis. Mitochondrial targeting of TR3, but not its DNA binding and transactivation, is essential for its proapoptotic effect. Our results reveal a mechanism by which a nuclear transcription factor translocates to mitochondria to initiate apoptosis.
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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Cell Fractionation
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Cell Nucleus / metabolism
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Cytochrome c Group / metabolism*
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DNA / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fatty Acids, Unsaturated / pharmacology
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Genes, Reporter
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Humans
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Intracellular Membranes / metabolism
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Intracellular Membranes / physiology
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Mitochondria / metabolism*
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Mutation
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Protein Structure, Tertiary
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Recombinant Fusion Proteins / metabolism
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
Substances
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Cytochrome c Group
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DNA-Binding Proteins
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Fatty Acids, Unsaturated
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NR4A1 protein, human
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Recombinant Fusion Proteins
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Transcription Factors
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DNA
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leptomycin B