The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues
The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues
复制标题
准金属亚砷酸盐可能通过与 N 端半胱氨酸残基结合诱导 Id3 的核输出
DOI：
10.1016/j.bbrc.2013.03.027
复制
发表时间：
2013
影响因子：
3.1
通讯作者：
Y.
中科院分区：
文献类型：
--
作者：
Kurooka;H.;Sugai;M.;Mori;K. and Yokota;Y.
Id是调节细胞增殖和分化的多功能转录抑制因子，Id蛋白的适当亚细胞定位对其功能至关重要。我们以前确定了不同的功能核输出信号（NES）在Id 1和Id 2，但没有活跃的内斯已报告在Id 3。在这项研究中，我们发现，处理与应力诱导类金属亚砷酸盐导致的积累GFP标记的Id3在细胞质中。胞质蓄积受损的突变，在Id3 NES样序列类似的Id1内斯，位于HLH域的末端。它也被CRM1特异性核输出抑制剂来普霉素B（LMB）的共同治疗所阻断，但不与丝裂原活化蛋白激酶（MAPK）的抑制剂。重要的是，我们发现，紧密间隔的N-末端半胱氨酸残基的Id3与砷衍生物氧化苯胂（PAO）相互作用，是必不可少的亚砷酸盐诱导的细胞质积累，表明亚砷酸盐诱导CRM 1依赖的核出口的Id3通过结合到N-末端半胱氨酸。最后，我们证明，Id3显着抑制亚砷酸盐刺激的即时早期基因Egr-1的转录，这种抑制活性与亚砷酸盐诱导的核输出呈负相关。我们的研究结果表明，Id3可能参与亚砷酸盐的生物作用。
Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite.