STAT3 is enriched in nuclear bodies
STAT3 is enriched in nuclear bodies
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DOI：
10.1242/jcs.00833
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发表时间：
2004-01-15
影响因子：
4
通讯作者：
Müller-Newen, G
中科院分区：
文献类型：
--
作者：
Herrmann, A;Sommer, U;Müller-Newen, G
信号转导子和转录激活子3（STAT 3）是一种参与多种生物学功能的转录因子。在白细胞介素-6（IL-6）及相关细胞因子的信号转导中起重要作用。响应于IL-6刺激，STAT 3变得磷酸化并易位到细胞核中，在那里它结合到靶基因的增强子序列。我们发现活化的STAT 3在细胞核内的点状结构中富集，我们称之为STAT 3核体。为了研究STAT 3核体形成的动力学，构建了STAT 3和黄色荧光蛋白（YFP）的融合蛋白。在活细胞中的研究表明，STAT 3核体的出现是短暂的，与STAT 3的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，核小体内的STAT 3由高度移动的和不移动的部分组成。共定位研究提供的证据表明，这些机构伴随着CREB结合蛋白（CBP）和乙酰化组蛋白H4，这是转录活性染色质的标记。此外，在HepG 2细胞中的STAT 3核小体不与含有早幼粒细胞白血病癌蛋白（PML）的小体共定位;也不能检测到活化的STAT 3的SUMO化。综上所述，我们的数据表明，STAT 3核体直接参与活性基因转录，或者它们作为活化的STAT 3的储存库。
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.