Three distinct domains contribute to nuclear transport of murine Foxp3.
Three distinct domains contribute to nuclear transport of murine Foxp3.
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DOI：
10.1371/journal.pone.0007890
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发表时间：
2009-11-18
期刊：
影响因子：
3.7
通讯作者：
Ozkaynak E
中科院分区：
文献类型：
--
作者：
Hancock WW;Ozkaynak E
Foxp3是一种47 kDa的转录因子，对CD4+CD25+调节性T细胞(Tregs)的功能是必需的，在控制自身反应性T细胞和防止自身免疫中起着重要作用。通过TCR参与激活Tregs导致Foxp3表达上调，随后其快速的核运输和与染色质的结合。在这里，我们确定了三个不同的Foxp3结构域，它们有助于核运输。第一个结构域(结构域1)由C端12个氨基酸组成。第二个结构域(结构域2)位于叉头结构域(FHD)的N端，最近报道该结构域是矮小相关转录因子1/急性髓系白血病1(RUNX1/AML1)的结合部位。第三个结构域(结构域3)位于前51个氨基酸的N末端。与已知的核定位信号(NLSS)不同，这三个区域都不富含碱性残基，也不与已知的具有一个或多个碱性氨基酸簇的单组分或双组分NLSS有任何相似之处。精氨酸-赖氨酸-赖氨酸-精氨酸(RKKR)序列位于Foxp3 C-末端的12-aa处，是几种蛋白质的核定位信号(NLS)，包括GFP-Foxp3杂交蛋白质。这里提供的证据表明，在全长的天然Foxp3中，RKKR不起NLS的作用。这项研究中报道的数据表明，Foxp3通过与其他核因子结合并与它们共同运输到细胞核来实现核转运。
Foxp3, a 47-kDa transcription factor, is necessary for the function of CD4+CD25+ regulatory T cells (Tregs), with an essential role in the control of self-reactive T cells and in preventing autoimmunity. Activation of Tregs by TCR engagement results in upregulation of Foxp3 expression, followed by its rapid nuclear transport and binding to chromatin. Here, we identify three distinct Foxp3 domains that contribute to nuclear transport. The first domain (Domain 1) comprises the C-terminal 12 amino acids. The second domain (Domain 2) is located immediately N-terminal to the forkhead domain (FHD), recently reported to be a binding site for the runt-related transcription factor 1/acute myeloid leukemia 1 (Runx1/AML1). The third domain (Domain 3) is located within the N-terminal first 51 amino acids. Unlike the known nuclear localization signals (NLSs), none of these three regions are rich in basic residues and do not bear any similarity to known monopartite or bipartite NLSs that have one or more clusters of basic amino acids. The basic arginine-lysine-lysine-arginine (RKKR) sequence, located 12-aa from the C-terminal end of Foxp3 was previously reported to be a nuclear localization signal (NLS) for several proteins, including for a GFP-Foxp3 hybrid. Evidence is provided here that in the full-length native Foxp3 RKKR does not function as an NLS. The data reported in this study indicates that Foxp3 achieves nuclear transport by binding to other nuclear factors and co-transporting with them to the nucleus.
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DOI：
10.1073/pnas.0700298104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Li, Bin;Samanta, Arabinda;Greene, Mark I.
通讯作者：
Greene, Mark I.
影响因子：
64.8
作者：
KALDERON, D;RICHARDSON, WD;SMITH, AE
通讯作者：
SMITH, AE
影响因子：
64.5
作者：
Wu, Yongqing;Borde, Madhuri;Rao, Anjana
通讯作者：
Rao, Anjana
影响因子：
4.4
作者：
Zhou, Zhaocai;Song, Xiaomin;Greene, Mark I.
通讯作者：
Greene, Mark I.
影响因子：
64.8
作者：
Ono, Masahiro;Yaguchi, Hiroko;Sakaguchi, Shimon
通讯作者：
Sakaguchi, Shimon