Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection.

Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection.
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DOI:
10.1038/ni.1769
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发表时间:
2009-08
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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CD 4 + CD 8+双阳性胸腺细胞中的T细胞受体信号传导决定细胞存活和谱系定型,但这一过程的遗传和分子基础尚不清楚。为了解决这个问题,我们使用乙基亚硝基脲诱变,以确定一个新的T-谱系特异性基因,Themis,这是完成正向选择的关键。Themis包含一个独特的球状结构域(CABIT)的串联重复序列,其中包括一个半胱氨酸基序,定义了一个由5个未表征的脊椎动物蛋白组成的家族,在大多数动物物种中具有直系同源物。Themis缺陷型胸腺细胞在早期T细胞受体信号传导中没有表现出重大损害,但在阳性选择之前和期间表现出细胞周期和存活基因表达的改变。这些数据表明,忒弥斯在维持积极的选择中发挥着独特的作用。
T-cell receptor signaling in CD4+CD8+ double positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a novel T-lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (CABIT), which includes a cysteine motif that defines a family of 5 uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no major impairment in early T-cell receptor signaling, but exhibited altered expression of cell cycle and survival genes before and during positive selection. These data suggest a unique role for Themis in sustaining positive selection.
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