DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development
DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development
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DOI：
10.1073/pnas.96.14.7992
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Martínez, C
中科院分区：
文献类型：
--
作者：
García-Domingo, D;Leonardo, E;Martínez, C
DIO-1（death inducer-obliterator-1）基因通过差异显示PCR在经历凋亡的前B WOL-1细胞中鉴定，编码一种推定的转录因子，其蛋白质具有两个锌指基序、核定位信号和转录激活结构域，在发育期间在肢指状交错网中表达。当过表达时，DIO-1易位到细胞核并在体外激活细胞凋亡。核定位序列缺失后，细胞核转位以及细胞凋亡的诱导均丧失。DIO-1细胞凋亡诱导被caspase抑制剂和Bcl-2过表达所阻止。通过在鸡肢体发育过程中错误表达DIO-1来研究DIO-1的体内作用。最常观察到的表型是肢体生长停滞，这种效应与参与这一过程的中胚层和外胚层基因的抑制相关。我们的数据表明DIO-1在体外触发凋亡过程的能力，并表明该基因在发育过程中的细胞死亡中的作用。
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.