DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development.
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.
García-Domingo
D
D
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autónoma, Campus de Cantoblanco, E-28049 Madrid, Spain.
Leonardo
E
E
Grandien
A
A
Martínez
P
P
Albar
J P
JP
Izpisúa-Belmonte
J C
JC
Martínez-A
C
C
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D002642:Chick Embryo; D004268:DNA-Binding Proteins; D004475:Ectoderm / Q000502:physiology; D004627:Embryonic Induction; D005314:Embryonic and Fetal Development; D005047:Etoposide / Q000494:pharmacology; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018878:Limb Buds / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016335:Zinc Fingers
C518584:DIDO1 protein, human; D004268:DNA-Binding Proteins; C120687:Dido protein, mouse; D014157:Transcription Factors; D005047:Etoposide