Novel nuclear localization signal regulated by ambient tonicity in vertebrates
Novel nuclear localization signal regulated by ambient tonicity in vertebrates
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DOI：
10.1074/jbc.m710550200
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发表时间：
2008-08-15
影响因子：
4.8
通讯作者：
Kwon, H. Moo
中科院分区：
文献类型：
--
作者：
Kwon, Min Seong;Do Lee, Sang;Kwon, H. Moo
TonEBP是一种含有Rel结构域的转录因子，与适应性免疫、病毒复制和癌症有关。在哺乳动物肾脏中，TonEBP是水稳态的中心调节剂。缺乏TonEBP的动物由于肾失水而遭受危及生命的脱水。环境张力（有效渗透压摩尔浓度）是TonEBP以双向方式的显著信号; TonEBP活性在低渗时降低，而在高渗时增加。在这里，我们发现，TonEBP显示核输出响应低渗和核输入响应高渗。TonEBP的核输出不受核输出受体CRM 1或离散核输出信号的介导。相反，在16个氨基酸残基的小区域中发现了显性核定位信号（NLS）。当含有NLS的短肽与组成型胞质蛋白融合时，融合蛋白显示出像TonEBP那样的张力依赖性核质运输。因此，NLS的张力依赖性激活在TonEBP的核质运输中至关重要。新型NLS仅存在于脊椎动物中，表明它在进化后期发展。
TonEBP is a Rel domain-containing transcription factor implicated in adaptive immunity, viral replication, and cancer. In the mammalian kidney, TonEBP is a central regulator of water homeostasis. Animals deficient in TonEBP suffer from life-threatening dehydration due to renal water loss. Ambient tonicity (effective osmolality) is the prominent signal for TonEBP in a bidirectional manner; TonEBP activity decreases in hypotonicity, whereas it increases in hypertonicity. Here we found that TonEBP displayed nuclear export in response to hypotonicity and nuclear import in response to hypertonicity. The nuclear export of TonEBP was not mediated by the nuclear export receptor CRM1 or discrete nuclear export signal. In contrast, a dominant nuclear localization signal (NLS) was found in a small region of 16 amino acid residues. When short peptides containing the NLS were fused to constitutively cytoplasmic proteins, the fusion proteins displayed tonicity-dependent nucleocytoplasmic trafficking like TonEBP. Thus, tonicity-dependent activation of the NLS is crucial in the nucleocytoplasmic trafficking of TonEBP. The novel NLS is present only in the vertebrates, indicating that it developed late in evolution.