Different localization of Hsp105 family proteins in mammalian cells.
Different localization of Hsp105 family proteins in mammalian cells.
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DOI：
10.1016/j.yexcr.2007.06.009
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发表时间：
2007-10
影响因子：
3.7
通讯作者：
Youhei Saito;N. Yamagishi;T. Hatayama
中科院分区：
文献类型：
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作者：
Youhei Saito;N. Yamagishi;T. Hatayama
HSP 105家族的HSP 105 α和HSP 105 β是来源于HSP 105基因转录物的可变剪接产物。Hsp105 α是组成性表达的，也可被各种应激诱导表达，而Hsp105 β缺少Hsp105 α的44个氨基酸，在轻度热休克时特异性表达。虽然Hsp105 α定位于哺乳动物细胞的细胞质中，但Hsp105 β的细胞定位尚不清楚。在这项研究中，我们发现Hsp105 β定位于细胞核，而不是细胞质Hsp105 α，这表明这些蛋白质在细胞的不同细胞区室中发挥作用。利用Hsp105 α和Hsp105 β的缺失和替换突变体，我们发现这些蛋白具有功能性核定位信号（NLS）和核输出信号（内斯）。此外，当用NES依赖的核输出的特异性抑制剂leptomycin B处理时，Hsp 105 α在细胞核中积累。importin β是NLS依赖性核转运的重要组成部分，siRNA可抑制Hsp105 β的核定位。此外，在Hsp105 α中发现而在Hsp105 β中未发现的44个氨基酸序列抑制NLS活性。因此，Hsp105 α和Hsp105 β的不同定位被认为是由于Hsp105 α抑制NLS活性。
Hsp105α and Hsp105β of the HSP105 family are alternatively spliced products derived from an hsp 105 gene transcript. Hsp105α is constitutively expressed and also induced by various stress, whereas Hsp105β, lacking 44 amino acids from Hsp105α, is specifically expressed during mild heat shock. Although Hsp105α is shown to localize in the cytoplasm of mammalian cells, cellular localization of Hsp105β is not known. In this study, we showed that Hsp105β localized in the nucleus of cells in contrast to cytoplasmic Hsp105α, suggesting that these proteins function in different cellular compartments of cells. Using deletion and substitution mutants of Hsp105α and Hsp105β, we revealed that these proteins had a functional nuclear localization signal (NLS) and a nuclear export signal (NES). Furthermore, Hsp105α accumulated in the nucleus of cells when treated with leptomycin B, a specific inhibitor of NES-dependent nuclear export. siRNA for importin β, an essential component for NLS-dependent nuclear transport, inhibited the nuclear localization of Hsp105β. Furthermore, the 44 amino acids sequence found in Hsp105α but not in Hsp105β suppressed the NLS activity. Thus, the different localization of Hsp105α and Hsp105β is suggested to be due to the suppressed NLS activity in Hsp105α.