PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors.

PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors.
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DOI:
10.1084/jem.20101156
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发表时间:
2010-07-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
von Boehmer H
von Boehmer H
中科院分区:
其他
文献类型:
--
作者:
Merkenschlager M;von Boehmer H

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调节性T(Treg)细胞相关转录因子Foxp3的表达可由T细胞受体(TCR)、白细胞介素 - 2(IL - 2)和转化生长因子(TGF)-β的信号诱导。这些信号通过一个涉及磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(PKB;此处称为Akt)和哺乳动物雷帕霉素靶蛋白(mTOR)的网络进行整合。新的研究表明,被Akt灭活的Foxo蛋白Foxo1和Foxo3a可驱动Foxp3表达。因此,这些研究解释了PI3K信号对Foxp3的负向调节作用,并将Foxo蛋白添加到了能够调节Foxp3表达的不断增加的核因子列表中。
Expression of the regulatory T (T reg) cell–associated transcription factor Foxp3 can be induced by signals from the T cell receptor (TCR), interleukin-2 (IL-2), and transforming growth factor (TGF)-β. These signals are integrated by a network involving phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB; here referred to as Akt), and the mammalian target of rapamycin (mTOR). New studies show that the Foxo proteins Foxo1 and Foxo3a, which are inactivated by Akt, drive Foxp3 expression. These studies therefore explain the negative regulation of Foxp3 by PI3K signaling, and add Foxo proteins to the growing list of nuclear factors capable of modulating Foxp3 expression.
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