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

Abstract

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.

Identification of p53 regulators by genome-wide functional analysis

“…These phenotypes closely resemble alterations induced by misexpression of other proapoptotic genes, such as death inducerobliterator-1 (DIO-1; ref. 30) and are consistent with increased apoptosis in the apical ectodermal ridge and͞or underlying mesenchyme during development. Importantly, retroviral delivery of Hey1, Hes1, or Osr1 induced similar distal truncations in 26%, 31%, and 36% of embryos with n ϭ 21, 26, and 28, respectively (Fig.…”

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms

“…Northern blot analysis of human and murine Dido1 expression showed 3 different transcripts in most cell lines and tissues analyzed ( Figure 1A), the smallest of which was previously identified as DIO-1 (28). To identify the 2 larger transcripts, we searched the National Center for Biotechnology Information (NCBI) database for known nucleotide sequences similar to that of Dido1 and found a human clone (KIAA0333) whose 5′ but not 3′ end sequence was identical to that of the human Dido1 (hDido1) nucleotide (not shown).…”

“…A differential display approach was used to identify death inducer-obliterator 1 (DIO-1; also known as Dido1 and DATF) as a gene whose expression is upregulated early in apoptosis (28). Its predicted amino acid sequence comprises a glutamine-rich region, an acidic sequence, and a canonical bipartite nuclear localization signal (NLS) in the N terminal region, 2 Zn-finger motifs in the central region, and a C terminal lysine-rich sequence (28). Here we report the cloning of 2 additional human and murine Dido isoforms that result from alternative splicing of the same gene.…”

Dido disruption leads to centrosome amplification and mitotic checkpoint defects compromising chromosome stability

“…To generate a GFP-Dido1 fusion protein, the Dido1 ORF, flanked by BamHI and ApaI sites (43), was cloned into BglII and ApaI sites in the pGFP-C1 vector (BD Clontech, Mountain View, CA). Vectors expressing GFP-Dido2 and -Dido3 fusions were constructed by replacing an internal BglII-NotI fragment with Dido2-or Dido3-specific parts.…”