NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun
NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun
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DOI：
10.1073/pnas.96.13.7214
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发表时间：
1999-06-22
影响因子：
11.1
通讯作者：
Rao, A
中科院分区：
文献类型：
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作者：
López-Rodríguez, C;Aramburu, J;Rao, A
NFAT转录因子与NF-kappa B/Rel蛋白相关，并与DNA上的Fos和Jun形成协同复合体。我们已经鉴定出一种NFAT相关蛋白NFAT5，它在结构、DNA结合和调控方面与传统的NFAT蛋白NFAT1-4不同。NFAT5含有一个类似于nfat的Rel同源结构域，保存了NFAT1-4的DNA接触残基，并结合了类似于在已明确表征的nfat依赖基因的调控区域发现的DNA序列。然而，它缺乏大多数Fos/Jun接触残基，不能与Fos和Jun合作结合到DNA上。与NFAT1-4不同，NFAT1-4的核输入受到钙调磷酸酶介导的去磷酸化的严格调节，NFAT5是一个组成核磷酸化蛋白，而不管钙调磷酸酶是否激活。这些特征表明，与传统的NFAT蛋白不同，NFAT1-4通过整合钙/钙调磷酸酶和蛋白激酶C/丝裂原激活的蛋白激酶信号通路的输入来激活基因转录，NFAT5参与了多种免疫和非免疫细胞中尚未确定的信号通路。
NFAT transcription factors are related to NF-kappa B/Rel proteins and form cooperative complexes with Fos and Jun on DNA. We have identified an NFAT-related protein, NFAT5, which differs from the conventional NFAT proteins NFAT1-4 in its structure, DNA binding, and regulation. NFAT5 contains a NFAT-like Rel homology domain, conserves the DNA contact residues of NFAT1-4, and binds DNA sequences similar to those found in the regulatory regions of well-eharacterized NFAT-dependent genes. However, it lacks the majority of Fos/Jun contact residues and does not bind cooperatively with Fos and Jun to DNA. Unlike NFAT1-4 whose nuclear import is tightly regulated by calcineurin-mediated dephosphorylation, NFAT5 is a constitutively nuclear phosphoprotein regardless of calcineurin activation. These features suggest that unlike the conventional NFAT proteins, NFAT1-4, which activate gene transcription by integrating inputs from calcium/calcineurin and protein kinase C/mitogen-activated protein kinase signaling pathways, NFAT5 participates in as-yet-unidentified signaling pathways in diverse immune and nonimmune cells.