Herrmann Andreas, Sommer Ulrike, Pranada Albert L, Giese Bernd, Küster Andrea, Haan Serge, Becker W, Heinrich Peter C, Müller-Newen Gerhard
Institut für Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
J Cell Sci. 2004 Jan 15;117(Pt 2):339-49. doi: 10.1242/jcs.00833. Epub 2003 Dec 2.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is involved in a variety of biological functions. It is essential for the signal transduction of interleukin-6 (IL-6) and related cytokines. In response to IL-6 stimulation STAT3 becomes phosphorylated and translocates into the nucleus where it binds to enhancer sequences of target genes. We found that activated STAT3 is enriched in dot-like structures within the nucleus, which we termed STAT3 nuclear bodies. To examine the dynamics of STAT3 nuclear body formation, a fusion protein of STAT3 and yellow fluorescent protein (YFP) was constructed. Studies in living cells have shown that the appearance of STAT3 nuclear bodies is transient, correlating with the timecourse of tyrosine-phosphorylation of STAT3. Furthermore, we show by fluorescence recovery after photobleaching (FRAP) analysis that STAT3 within nuclear bodies consists of a highly mobile and an immobile fraction. Colocalization studies provided evidence that these bodies are accompanied with CREB binding protein (CBP) and acetylated histone H4, which are markers for transcriptionally active chromatin. Moreover, STAT3 nuclear bodies in HepG2 cells are not colocalized with promyelocytic leukemia oncoprotein (PML)-containing bodies; neither is a sumoylation of activated STAT3 detectable. Taken together, our data suggest that STAT3 nuclear bodies are either directly involved in active gene transcription or they serve as reservoirs of activated STAT3.
信号转导及转录激活因子3（STAT3）是一种参与多种生物学功能的转录因子。它对于白细胞介素-6（IL-6）及相关细胞因子的信号转导至关重要。在受到IL-6刺激后，STAT3发生磷酸化并转位进入细胞核，在细胞核中它与靶基因的增强子序列结合。我们发现活化的STAT3在细胞核内的点状结构中富集，我们将其称为STAT3核体。为了研究STAT3核体形成的动力学，构建了STAT3与黄色荧光蛋白（YFP）的融合蛋白。对活细胞的研究表明，STAT3核体的出现是短暂的，与STAT3酪氨酸磷酸化的时间进程相关。此外，我们通过光漂白后荧光恢复（FRAP）分析表明，核体内的STAT3由高迁移率部分和固定部分组成。共定位研究提供了证据，表明这些核体与CREB结合蛋白（CBP）和乙酰化组蛋白H4相伴，它们是转录活性染色质的标志物。此外，HepG2细胞中的STAT3核体与含早幼粒细胞白血病癌蛋白（PML）的小体不共定位；活化的STAT3也未检测到有SUMO化修饰。综上所述，我们的数据表明，STAT3核体要么直接参与活跃的基因转录，要么作为活化STAT3的储存库。
