Death inducer-obliterator 1 triggers apoptosis after nuclear translocation and caspase upregulation.
Death inducer-obliterator 1 (DIO-1) is a gene that is upregulated early in apoptosis. Here we report that in healthy cells, the DIO-1 gene product was located in the cytoplasm, where it formed oligomers. After interleukin-3 starvation or c-Myc-induced apoptosis in serum-free conditions, DIO-1 translocated to the nucleus, where it upregulated caspase levels and activity. A nuclear localization signal deletion mutant (DIO-1deltaNLS) was unable to translocate to the nuclear compartment in the absence of interleukin-3 and failed to upregulate procaspase levels or trigger cell death. In addition, cells stably expressing DIO-1deltaNLS were protected from apoptosis induced by interleukin-3 withdrawal. These results indicate that DIO-1 has a relevant role in regulating the early stages of cell death.
García-Domingo
David
D
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autonomo de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain.
Ramírez
Dorian
D
González de Buitrago
Gonzalo
G
Martínez-A
Carlos
C
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D009154:Mutation; D019913:Nuclear Localization Signals; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C518584:DIDO1 protein, human; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D007377:Interleukin-3; D019913:Nuclear Localization Signals; D014157:Transcription Factors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases