BINDING OF THE WILMS-TUMOR LOCUS ZINC FINGER PROTEIN TO THE EGR-1 CONSENSUS SEQUENCE
BINDING OF THE WILMS-TUMOR LOCUS ZINC FINGER PROTEIN TO THE EGR-1 CONSENSUS SEQUENCE
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DOI：
10.1126/science.2244209
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发表时间：
1990-11-30
期刊：
影响因子：
56.9
通讯作者：
CURRAN, T
中科院分区：
文献类型：
--
作者：
RAUSCHER, FJ;MORRIS, JF;CURRAN, T
Wilms' tumor locus（WTL）在11 p13处包含编码具有DNA结合蛋白特征的含锌指蛋白的基因。然而，这种蛋白质以序列特异性方式与DNA结合尚未得到证实。构建了含锌指区的合成基因，并在大肠杆菌中表达了该蛋白。重组蛋白用于从简并寡核苷酸池中鉴定特异性DNA结合位点。所获得的结合位点与早期生长反应-1（EGR-1）基因产物（一种由促有丝分裂刺激诱导的含锌指蛋白）识别的序列相似。最初在Wilms肿瘤患者中鉴定的蛋白质锌指区的突变消除了其DNA结合活性。这些结果表明WTL蛋白可能作用于生长因子诱导基因的DNA结合位点，并且DNA结合活性的丧失有助于致瘤过程。
The Wilms' tumor locus (WTL) at 11p13 contains a gene that encodes a zinc finger-containing protein that has characteristics of a DNA-binding protein. However, binding of this protein to DNA in a sequence-specific manner has not been demonstrated. A synthetic gene was constructed that contained the zinc finger region, and the protein was expressed inEscherichia coli. The recombinant protein was used to identify a specific DNA binding site from a pool of degenerate oligonucleotides. The binding sites obtained were similar to the sequence recognized by the early growth response-1 (EGR-1) gene product, a zinc finger-containing protein that is induced by mitogenic stimuli. A mutation in the zinc finger region of the protein originally identified in a Wilms' tumor patient abolished its DNA-binding activity. These results suggest that the WTL protein may act at the DNA binding site of a growth factor-inducible gene and that loss of DNA-binding activity contributes to the tumorigenic process.