STAT3入核的核定位序列研究  

Basic Amino Acid Enriching Element in DNA Binding Domain Has Critical Role in ST AT3 Nuclear Import

作　　者：叶中德[1] 沈倍奋[1] 黎燕[1] 

机构地区：[1]军事医学科学院基础医学研究所

出　　处：《生物化学与生物物理进展》2004年第1期32-35,共4页Progress In Biochemistry and Biophysics

基　　金：国家杰出青年科学基金资助项目 ( 3 992 5 0 19);国家重点基础研究发展规划项目 ( 973 ) ( 0 0 1CB5 10 0 0 5 )~~

摘　　要：STAT3(signaltransducersandactivatorsoftranscription)是胞浆中的潜在转录因子 ,在细胞因子、生长因子等外界信号分子的刺激下发生磷酸化和二聚化进入细胞核 ,结合在基因特定的启动子上调控转录 .目前对STAT3的磷酸化和二聚化都相当清楚 ,但对其怎样进入细胞核还知之甚少 .入核分子一般都有一段碱性氨基酸的核定位序列(NLS) ,但通过比较STAT家族没有发现经典的核定位序列 (NLS) .以IL 6为外界信号分子 ,2 93T为细胞模型 ,绿色荧光蛋白GFP为标签分子 ,研究发现STAT 3分子在IL 6刺激前呈胞浆分布 ,刺激后聚集胞核中是由于构象的改变暴露了核定位序列 .通过同源比较和缺失突变发现 ,位于STAT 3DNA结合域 4 0 3～ 4 2 6位氨基酸之间的一段富含赖氨酸和精氨酸的碱性氨基酸对STAT 3入核起重要作用 ,具有核定位序列 (NLS)Latent signal transducers and activators of transcrip tion(STATs) reside in the nucleus following cytokine stimulation and regulate gene expression upon activation of cytokine or growth factor receptors. While this translocation event is essential for gene regulation by STATs, their mechanism of transport through the cytoplasm to the nucleus has remained elusive. Nuclear shuttling molecules often own a mono or bipartite basic amino acid stretch, but ST AT family do not own the classic nuclear localization sequence(NLS). Now, it is reported that STAT3 accumulate nucleus after IL 6 stimulation 20 min. With IL 6 stimulation, STAT3 molecule conformation changed and the NLS in DNA binding domain exposure to make it gain nuclear targeting function. Deleted a stretch(403 ～426aa) of basic amino acid in STAT3 DNA binding domain which destroys the nuclear importing function even with cytokine stimulation. It indicated that this stretch of basic amino acid has critical role for STAT3 nuclear import, which has nuclear localization sequence(NLS)function.

关 键 词：STAT3 入核 核定位序列 转录因子 

分 类 号：Q756[生物学—分子生物学] Q26