Identification of inhibitor-of-differentiation 2 (Id2) as a modulator of neuronal apoptosis
Identification of inhibitor-of-differentiation 2 (Id2) as a modulator of neuronal apoptosis
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DOI：
10.1046/j.0022-3042.2002.00760.x
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发表时间：
2002-03-01
影响因子：
4.7
通讯作者：
Schulz, JB
中科院分区：
文献类型：
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作者：
Gleichmann, M;Buchheim, G;Schulz, JB
分化抑制因子2(Id2)是一类转录调节因子家族，具有螺旋环状螺旋结构域，但缺乏碱性氨基酸结构域。在发育过程中，Id2可能通过清除下游的E-box基本螺旋-环-螺旋蛋白来拮抗视网膜母细胞瘤蛋白介导的分化。在这里，利用差异显示RT-PCR，我们确定Id2是血清和缺钾诱导小脑颗粒神经元凋亡过程中的一个诱导基因。与诱导Id2信使RNA和蛋白表达在神经细胞死亡中的生物学作用一致，Id2反义RNA的表达，或Id2基因在Id2基因敲除小鼠神经元中的定向缺失，可以保护神经元免受凋亡。此外，基因转移介导的Id2过表达在高钾和低钾条件下均可诱导神经细胞死亡。因此，本研究明确了Id2在调节神经细胞凋亡中的作用。
Inhibitor-of-differentiation 2 (Id2) belongs to a family of transcriptional modulators that are characterized by a helix loop helix region but lack the basic amino acid domain. During development, Id2 antagonizes differentiation mediated by the retinoblastoma protein, probably by scavenging downstream E-box basic helix-loop-helix proteins. Here, using differential display RT-PCR, we identify Id2 as an induced gene during serum and potassium deprivation-induced apoptosis of cerebellar granule neurons. Consistent with a biological role for induced Id2 messenger RNA and protein expression in neuronal cell death, expression of Id2 antisense RNA, or targeted deletion of the Id2 gene in neurons from Id2 knockout mice, protect from apoptosis. Further, gene transfermediated overexpression of Id2 induces neuronal cell death both in high potassium and low potassium conditions. Thus, the present study defines a role for Id2 in the modulation of neuronal apoptosis.