Regulation of T helper type 2 cell differentiation by murine Schnurri-2.

Regulation of T helper type 2 cell differentiation by murine Schnurri-2.
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DOI:
10.1084/jem.20040733
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发表时间:
2005-02-07
影响因子:
15.3
通讯作者:
Nakayama, T
Nakayama, T
中科院分区:
医学1区
文献类型:
--
作者:
Kimura, MY;Hosokawa, H;Yamashita, M;Hasegawa, A;Iwamura, C;Watarai, H;Taniguchi, M;Takagi, T;Ishii, S;Nakayama, T

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Schnurri(Shn)是一种大型锌指蛋白,与细胞生长、信号转导和淋巴细胞发育有关。脊椎动物至少拥有三种Shn直系同源物(Shn - 1、Shn - 2和Shn - 3),它们似乎在骨形态发生蛋白、转化生长因子β和激活素信号通路中起作用。然而,Shn蛋白的生理功能在很大程度上仍然未知。在Shn - 2缺陷型小鼠中,成熟的外周T细胞表现出正常的抗T细胞受体诱导的增殖,尽管向T辅助细胞2型(Th2)细胞的分化显著增强,而对Th1细胞分化仅有轻微影响。Shn - 2缺陷的发育中的Th2细胞显示出核因子κB(NF - κB)的组成性激活以及GATA3诱导增强。Shn - 2能够与p50 NF - κB竞争结合共有NF - κB基序,并抑制NF - κB驱动的启动子活性。因此,Shn - 2通过调节NF - κB功能在控制Th2细胞分化中起关键作用。
Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor β, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2–deficient mice, mature peripheral T cells exhibited normal anti–T cell receptor–induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2–deficient developing Th2 cells showed constitutive activation of nuclear factor κB (NF-κB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-κB for binding to a consensus NF-κB motif and inhibit NF-κB–driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-κB function.
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