IAN family critically regulates survival and development of T lymphocytes.
IAN family critically regulates survival and development of T lymphocytes.
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Ian家族严格调节T淋巴细胞的生存和发展。
DOI：
10.1371/journal.pbio.0040103
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发表时间：
2006-04
期刊：
影响因子：
9.8
通讯作者：
Takahama, Yousuke
中科院分区：
文献类型：
--
作者：
Nitta, Takeshi;Nasreen, Mariam;Seike, Takafumi;Goji, Atsushi;Ohigashi, Izumi;Miyazaki, Tadaaki;Ohta, Tsutomu;Kanno, Masamoto;Takahama, Yousuke
IAN（免疫相关核苷酸结合蛋白）家族是功能未表征的 GTP 结合蛋白家族，在抗菌反应期间在脊椎动物免疫细胞和植物细胞中表达。在这里，我们表明，小鼠基因组单个簇中编码的所有八个 IAN 家族基因主要在淋巴细胞中表达，并且 IAN1、IAN4 和 IAN5 的表达在 T 淋巴细胞的胸腺选择后显着升高。功能获得实验表明，IAN1 的过早过度表达会杀死未成熟的胸腺细胞，而短发夹 RNA 介导的功能丧失研究表明，IAN4 支持正选择。 IAN5 的敲低扰乱了 CD4/CD8 双阳性胸腺细胞的最佳生成，并降低了成熟 T 淋巴细胞的存活率。我们还显示证据表明 IAN4 和 IAN5 与抗凋亡蛋白 Bcl-2 和 Bcl-xL 相关，而 IAN1 与促凋亡蛋白 Bax 相关。因此，IAN 家族是一个新的 T 细胞受体反应蛋白家族，它严格调节 T 淋巴细胞的胸腺发育和存活，并可能通过与 Bcl-2 家族蛋白的结合发挥调节功能。 作者描述了 IAN 蛋白（以前未表征的 GTP 结合蛋白家族）在 T 细胞发育中的新作用；不同的 IAN 蛋白在 T 细胞发育的不同阶段发挥着重要作用。
The IAN (immune-associated nucleotide-binding protein) family is a family of functionally uncharacterized GTP-binding proteins expressed in vertebrate immune cells and in plant cells during antibacterial responses. Here we show that all eight IAN family genes encoded in a single cluster of mouse genome are predominantly expressed in lymphocytes, and that the expression of IAN1, IAN4, and IAN5 is significantly elevated upon thymic selection of T lymphocytes. Gain-of-function experiments show that the premature overexpression of IAN1 kills immature thymocytes, whereas short hairpin RNA-mediated loss-of-function studies show that IAN4 supports positive selection. The knockdown of IAN5 perturbs the optimal generation of CD4/CD8 double-positive thymocytes and reduces the survival of mature T lymphocytes. We also show evidence suggesting that IAN4 and IAN5 are associated with anti-apoptotic proteins Bcl-2 and Bcl-xL, whereas IAN1 is associated with pro-apoptotic Bax. Thus, the IAN family is a novel family of T cell–receptor-responsive proteins that critically regulate thymic development and survival of T lymphocytes and that potentially exert regulatory functions through the association with Bcl-2 family proteins. The authors describe new roles for IAN proteins (a previously uncharacterized family of GTP binding proteins) in T cell development; different IAN proteins play important roles at distinct stages of T cell development.