Open AccessDIO-1is a gene involved in onset of apoptosisin vitro,whose misexpression disrupts limb development
Author(s) -
David GarcíaDomingo,
Esther Leonardo,
Alf Grandien,
Pedro Martínez,
Juan Pablo Albar,
Juan Carlos Izpisúa-Belmonte,
Carlos Martı́nez-A
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.14.7992
Subject(s) - biology , apoptosis , transcription factor , microbiology and biotechnology , gene , limb development , in vitro , phenotype , programmed cell death , gene expression , nuclear localization sequence , regulation of gene expression , nucleus , genetics
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.