A STAT PROTEIN DOMAIN THAT DETERMINES DNA-SEQUENCE RECOGNITION SUGGESTS A NOVEL DNA-BINDING DOMAIN
A STAT PROTEIN DOMAIN THAT DETERMINES DNA-SEQUENCE RECOGNITION SUGGESTS A NOVEL DNA-BINDING DOMAIN
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DOI：
10.1101/gad.9.8.984
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发表时间：
1995-04-15
影响因子：
10.5
通讯作者：
DARNELL, JE
中科院分区：
文献类型：
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作者：
HORVATH, CM;WEN, ZL;DARNELL, JE
Stat1和Stat3是配体激活的转录因子家族的两个成员，具有信号转导和转录激活的双重功能。虽然这两种蛋白质从随机寡核苷酸中选择非常相似（但不完全相同）的最佳结合位点，但在天然STAT结合位点上，它们结合亲和力的差异很明显。为了利用这些不同的亲和力，使用嵌合的Stat1:Stat3分子来定位能够区分一般结合位点和特定结合位点的氨基酸。在这些约750个氨基酸长的蛋白质中，类似于400到类似于500的残基之间的氨基酸决定了DNA结合位点的特异性。该区域内的突变导致Stat蛋白虽然能正常地被酪氨酸磷酸化激活并二聚化，但DNA结合亲和力大大降低。
Stat1 and Stat3 are two members of the ligand-activated transcription factor family that serve the dual functions of signal transducers and activators of transcription. Whereas the two proteins select very similar (not identical) optimum binding sites from random oligonucleotides, differences in their binding affinity were readily apparent with natural STAT-binding sites. To take advantage of these different affinities, chimeric Stat1:Stat3 molecules were used to locate the amino acids that could discriminate a general binding site from a specific binding site. The amino acids between residues similar to 400 and similar to 500 of these similar to 750-amino-acid-long proteins determine the DNA-binding site specificity. Mutations within this region result in Stat proteins that are activated normally by tyrosine phosphorylation and that dimerize but have greatly reduced DNA-binding affinities.