Abstract
Nur77 is a nuclear orphan steroid receptor that has been implicated in negative selection. Expression of Nur77 in thymocytes and cell lines leads to apoptosis through a mechanism that remains unclear. In some cell lines, Nur77 was reported to act through a transcription-independent mechanism involving translocation to mitochondria, leading to cytochrome c release. However, we show here that Nur77-mediated apoptosis in thymocytes does not involve cytoplasmic cytochrome c release and cannot be rescued by Bcl-2. Microarray analysis shows that Nur77 induces many genes, including two novel genes (NDG1, NDG2) and known apoptotic genes FasL and TRAIL. Characterization of NDG1 and NDG2 indicates that NDG1 initiates a novel apoptotic pathway in a Bcl-2-independent manner. Thus Nur77-mediated apoptosis in T cells involves Bcl-2 independent transcriptional activation of several known and novel apoptotic pathways.
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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Amino Acid Sequence
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Animals
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Apoptosis / physiology*
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Base Sequence
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Cells, Cultured
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Cloning, Molecular
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DNA Primers
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Escherichia coli / cytology
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Escherichia coli / genetics
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Escherichia coli / physiology
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Female
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Genotype
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Humans
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Sequence Data
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Oligonucleotide Array Sequence Analysis
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Pregnancy
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Rats
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Receptors, Antigen, T-Cell / physiology
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / physiology*
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcriptional Activation / genetics*
Substances
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DNA Primers
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DNA-Binding Proteins
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NR4A1 protein, human
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Nr4a1 protein, mouse
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Nr4a1 protein, rat
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Receptors, Antigen, T-Cell
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Transcription Factors