Crif1 is a novel transcriptional coactivator of STAT3
Crif1 is a novel transcriptional coactivator of STAT3
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DOI：
10.1038/sj.emboj.7601986
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发表时间：
2008-02-20
期刊：
影响因子：
11.4
通讯作者：
Kong, Young-Yun
中科院分区：
文献类型：
--
作者：
Kwon, Min-chul;Koo, Bon-Kyoung;Kong, Young-Yun
信号转导子和转录激活子3（STAT 3）是一种转录因子，其响应于各种刺激而执行广谱生物学功能。然而，没有特定的共激活因子，调节转录活性的STAT 3已被确定。在这里，我们报告说，CR 6相互作用因子1（Crif 1）是一个特定的转录共激活STAT 3，但不是STAT 1或STAT 5a。Crif 1与STAT 3相互作用并正向调节其转录活性。Crif 1（-/-）胚胎在胚胎第6.5天左右死亡，表现为发育停滞，伴有增殖缺陷和大量凋亡。STAT 3靶基因的表达在Crif 1（-/-）胚泡培养物和抑瘤素M刺激的Crif 1缺陷MEFs中显著降低。重要的是，组成型活性STAT 3-C的关键活动，如转录，DNA结合和细胞转化，在Crif 1无效的MEFs中被取消，这表明Crif 1在STAT 3的转录活性中的重要作用。我们的研究结果表明，Crif 1是一种新的和必要的转录共激活因子的STAT 3，调节其DNA结合能力，并揭示了致癌STAT 3的调节。
Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor that performs a broad spectrum of biological functions in response to various stimuli. However, no specific coactivator that regulates the transcriptional activity of STAT3 has been identified. Here we report that CR6-interacting factor 1 (Crif1) is a specific transcriptional coactivator of STAT3, but not of STAT1 or STAT5a. Crif1 interacts with STAT3 and positively regulates its transcriptional activity. Crif1(-/-) embryos were lethal around embryonic day 6.5, and manifested developmental arrest accompanied with defective proliferation and massive apoptosis. The expression of STAT3 target genes was markedly reduced in a Crif1(-/-) blastocyst culture and in Oncostatin M-stimulated Crif1-deficient MEFs. Importantly, the key activities of constitutively active STAT3-C, such as transcription, DNA binding, and cellular transformation, were abolished in the Crif1-null MEFs, suggesting the essential role of Crif1 in the transcriptional activity of STAT3. Our results reveal that Crif1 is a novel and essential transcriptional coactivator of STAT3 that modulates its DNA binding ability, and shed light on the regulation of oncogenic STAT3.