DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development

Stockholm University, Tukholma, Stockholm, Sweden
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/1999; 96(14):7992-7. DOI: 10.1073/pnas.96.14.7992
Source: PubMed


The DIO-1 (death inducer-obliterator-1) gene, identified by differential display PCR in pre-B WOL-1 cells undergoing apoptosis, encodes a putative transcription factor whose protein has two Zn finger motifs, nuclear localization signals, and transcriptional activation domains, expressed in the limb interdigitating webs during development. When overexpressed, DIO-1 translocates to the nucleus and activates apoptosis in vitro. Nuclear translocation as well as induction of apoptosis are lost after deletion of the nuclear localization sequences. DIO-1 apoptotic induction is prevented by caspase inhibitors and Bcl-2 overexpression. The in vivo role of DIO-1 was studied by misexpressing DIO-1 during chicken limb development. The most frequently observed phenotype was an arrest in limb outgrowth, an effect that correlates with the inhibition of mesodermal and ectodermal genes involved in this process. Our data demonstrate the ability of DIO-1 to trigger apoptotic processes in vitro and suggest a role for this gene in cell death during development.

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    • "Active caspase-8 initiates a cascade of caspases which mediate apoptosis [25]. Another example is a large increase in the expression of DIO-1 (death inducer-obliterator-1) that translocates to the nucleus and activates apoptosis in cell culture [26]. KIAA1199 knockdown also led to up-regulation of A-kinase anchor protein 8 (AKAP95) that is a potential carrier protein for active caspase 3, carrying it from the cytoplasm into the nuclei in apoptotic cells and is involved in the process of apoptotic nuclear morphological change [27]. "
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    • "DIO-1 was identified by differential display PCR in pre-B WOL-1 cells undergoing apoptosis by interleukin-7 (IL-7) starvation. The DIO-1 gene is located at 20q13.33 in Homo sapiens, and its amino acid sequence exhibits predicted transcriptional activation domains consisting of a canonical bipartite nuclear localization signal (NLS) in the N-terminal region, two Zn-finger motifs in the central region, and a C-terminal lysine-rich sequence49. The expression level of DIO-1 is low in WOL-1 cells in the logarithmic growth period. "
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    • "Certain of the downregulated genes were associated with apoptosis, including the death inducer-obliterator 1 (DIDO1) , fibroblast growth factor receptor 3 (FGFR3) , and CD24 (Table 2) . DIDO1 is upregulated at an early stage in apoptotic cell death (Garcia-Domingo et al., 1999) . FGFR3 knockdown in human bladder carcinoma cells induces cellcycle progression arrest and influences tumorigenesis (Qing et al., 2009) . "
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