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Molecular and Cellular Biology, May 2003, p. 3216-3225, Vol. 23, No. 9
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.9.3216-3225.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Death Inducer-Obliterator 1 Triggers Apoptosis after Nuclear Translocation and Caspase Upregulation

David García-Domingo, Dorian Ramírez,{dagger} Gonzalo González de Buitrago, and Carlos Martínez-A*

Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autonomo de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain

Received 22 July 2002/ Returned for modification 4 September 2002/ Accepted 4 February 2003

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-1{Delta}NLS) 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-1{Delta}NLS 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.

* Corresponding author. Mailing address: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, E-28049 Madrid, Spain. Phone: 34 91 585 45 59. Fax: 34 91 372 04 93. E-mail: cmartineza{at}cnb.uam.es.

{dagger} Present address: University of Michigan Medical School, Ann Arbor, MI 48109.

Molecular and Cellular Biology, May 2003, p. 3216-3225, Vol. 23, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.9.3216-3225.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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