RAPID ACTIVATION BY INTERFERON-ALPHA OF A LATENT DNA-BINDING PROTEIN PRESENT IN THE CYTOPLASM OF UNTREATED CELLS
RAPID ACTIVATION BY INTERFERON-ALPHA OF A LATENT DNA-BINDING PROTEIN PRESENT IN THE CYTOPLASM OF UNTREATED CELLS
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DOI：
10.1073/pnas.86.4.1203
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发表时间：
1989-02-01
影响因子：
11.1
通讯作者：
STARK, GR
中科院分区：
文献类型：
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作者：
DALE, TC;IMAM, AMA;STARK, GR
人类基因6-16和9-27的高度保守的干扰素刺激的调节元件与人Bristol 8B细胞或经干扰素-α处理的人包皮成纤维细胞提取液中检测到的一种或多种蛋白质(E因子)结合。在未经处理的细胞的提取物中检测不到E因子，并在1分钟内以低盐可提取的形式出现在经干扰素处理的细胞中，因此推测不与DNA结合。几分钟后，这种形式的水平下降，同时增加了一种只能用高盐提取的形式，因此推测它与DNA结合。干扰素-α对E因子的诱导作用在无核的胞质中可以检测到E因子，而在干扰素处理的核母细胞中没有检测到E因子。综上所述，这些结果提示了一种信号转导模型，在该模型中，位于细胞质中的潜伏E因子在与干扰素-α结合后非常迅速地被激活或从抑制剂中释放。它的感受器。然后，活性E因子可以迁移到细胞核，在那里它与干扰素调节基因的干扰素刺激调节元件结合，激活它们的转录。
The highly conserved interferon (IFN)-stimulated regulatory elements of the human genes 6-16 and 9-27 bind to one or more proteins (E factor) detected in extracts of human Bristol 8 B cells or human foreskin fibroblast cells treated with IFN-.alpha.. E factor is not detectable in extracts of untreated cells and appears in IFN-treated cells within < 1 min in a form extractable with low salt and thus presumably not bound to DNA. After a few more minutes, the level of this form decreases in parallel with the increase of a form extractable only with high salt and thus presumably bound to DNA. Induction of E factor by IFN-.alpha. can occur in nuclei-free cytoplasts, whereas no E factor was detected in IFN-treated nucleoplasts. Together, these results suggest a model for signal transduction in which latent E factor, located in the cytoplasm, is activated or released from an inhibitor very rapidly upon binding of IFN-.alpha. to its receptor. Active E factor can then migrate to the nucleus, where it binds to the IFN-stimulated regulatory elements of IFN-regulated genes, activating their transcription.