Abstract
The orphan nuclear receptor Nur77 has been implicated in both growth and apoptosis, and its function and activity can be modulated by cellular redistribution. Green fluorescent protein-tagged Nur77 was used to evaluate the role of Nur77 intracellular redistribution in response to genotoxic stress. Selected DNA damaging agents and transcription inhibition lead to rapid redistribution of Nur77 into nuclear structures distinct from conventional nuclear bodies. These nuclear bodies formed transiently were tightly bound to the nuclear matrix and conditions that lead to their appearance were associated with Nur77 transcriptional inhibition. The formation of Nur77 nuclear bodies might be involved in programmed cell death modulation upon exposure to DNA damaging agents that inhibit transcription by sequestrating this proapoptotic factor in dense nuclear structures.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / genetics
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Camptothecin / pharmacology
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Cell Line
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Cell Line, Tumor
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Cell Nucleus / chemistry
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism*
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Cisplatin / pharmacology
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Cyclic AMP Response Element-Binding Protein / analysis
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DNA Damage*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Etoposide / pharmacology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Humans
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Microscopy, Confocal
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Mutation / genetics
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Neoplasm Proteins / analysis
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Neoplasm Proteins / metabolism
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Nerve Tissue Proteins / analysis
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Nuclear Matrix / drug effects
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Nuclear Matrix / metabolism
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Nuclear Proteins / analysis
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Nuclear Proteins / metabolism
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Phosphoproteins / analysis
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Promyelocytic Leukemia Protein
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Protein Binding
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RNA-Binding Proteins / analysis
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Steroid / genetics
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Receptors, Steroid / metabolism*
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SMN Complex Proteins
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Serine-Arginine Splicing Factors
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics*
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Transfection
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Tumor Suppressor Proteins / analysis
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Tumor Suppressor Proteins / metabolism
Substances
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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NR4A1 protein, human
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Neoplasm Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Nucleic Acid Synthesis Inhibitors
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Phosphoproteins
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Promyelocytic Leukemia Protein
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RNA-Binding Proteins
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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SMN Complex Proteins
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SRSF8 protein, human
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Transcription Factors
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Tumor Suppressor Proteins
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PML protein, human
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Green Fluorescent Proteins
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Serine-Arginine Splicing Factors
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Etoposide
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Cisplatin
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Camptothecin