Nur77 forms novel nuclear structures upon DNA damage that cause transcriptional arrest.
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.
INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval (QC), Canada H7V 1B7.
Louis
L
de Léséleuc
François
F
Denis
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis; D015530:Nuclear Matrix / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010750:Phosphoproteins / Q000032:analysis; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D055532:SMN Complex Proteins; D000068103:Serine-Arginine Splicing Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D019384:Nucleic Acid Synthesis Inhibitors; D010750:Phosphoproteins; D000071156:Promyelocytic Leukemia Protein; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D055532:SMN Complex Proteins; C000595776:SRSF8 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D049452:Green Fluorescent Proteins; D000068103:Serine-Arginine Splicing Factors; D005047:Etoposide; D002945:Cisplatin; D002166:Camptothecin