Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-α
Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-α
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DOI：
10.1093/emboj/21.7.1754
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发表时间：
2002-04-02
期刊：
影响因子：
11.4
通讯作者：
Reich, NC
中科院分区：
文献类型：
--
作者：
McBride, KM;Banninger, G;Reich, NC
信号转导子和转录激活子（STAT）以潜伏状态存在于细胞的细胞质中，但响应于细胞因子或生长因子而在细胞核中积累。在STAT酪氨酸磷酸化和二聚化之后发生在细胞核中的定位。在这份报告中，我们证明了一个直接的相互作用的输入-α 5与酪氨酸磷酸化的STAT 1二聚体，并提供证据表明，核定位信号（NLS）存在于一个STAT 1单体内的非活性状态。STAT 1亮氨酸407（L407 A）的突变的特点是，它产生的蛋白质是准确的酪氨酸磷酸化的干扰素，二聚化和结合DNA，但不定位于细胞核。STAT 1（L407 A）的输入缺陷似乎是这种蛋白不能被其输入穿梭受体识别的结果。此外，我们证明STAT 1与特定靶DNA的结合有效地阻断了importin-alpha 5结合。这一结果可能在将STAT 1定位到其在细胞核中的目的地以及从STAT 1释放importin-alpha 5方面发挥作用。再循环回细胞质。
Signal transducers and activators of transcription (STATs) reside in a latent state in the cytoplasm of the cell, but accumulate in the nucleus in response to cytokines or growth factors. Localization in the nucleus occurs following STAT tyrosine phosphorylation and dimerization. In this report we demonstrate a direct interaction of importin-alpha5 with tyrosine-phosphorylated STAT1 dimers, and provide evidence that a nuclear localization signal (NLS) exists in an inactive state within a STAT1 monomer. A mutation in STAT1 leucine 407 (L407A) is characterized, which generates a protein that is accurately tyrosine phosphorylated in response to interferon, dimerizes and binds DNA, but does not localize to the nucleus. The import defect of STAT1(L407A) appears to be a consequence of the inability of this protein to be recognized by its import shuttling receptor. In addition, we demonstrate that STAT1 binding to specific target DNA effectively blocks importin-alpha5 binding. This result may play a role in localizing STAT1 to its destination in the nucleus, and in releasing importin-alpha5 from STAT1. for recycling back to the cytoplasm.