DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150(Sal2).

DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150(Sal2).
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DOI:
10.1016/j.bbagrm.2011.02.002
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发表时间:
2011-04
影响因子:
4.7
通讯作者:
Benjamin, Thomas
Benjamin, Thomas
中科院分区:
生物学2区
文献类型:
--
作者:
Gu, Hongcang;Li, Dawei;Sung, Chang K.;Yim, Hyungshin;Troke, Philip;Benjamin, Thomas

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SALL 2蛋白p150 Sal 2的产物是具有与p53重叠的生长停滞和促凋亡功能的多锌指转录因子。它的DNA结合特性是未知的。我们已经使用了一种改进的SELEX程序与纯化的p150 Sal 2和随机序列的寡核苷酸池,以确定那些优先结合p150 Sal 2。体外最佳结合的共有序列是GGG(T/C)GGG,将p150 Sal 2置于包括Sp1家族转录因子在内的一大组GC盒结合蛋白中。p150 Sal 2中类似于Sp1中的三重锌指基序是DNA结合所必需的。p150 Sal 2和Sp1显示出体外协同结合和体内相互作用的证据。p150 Sal 2是已知的CDK抑制剂p21 Cip 1/Waf 1(p21)的激活剂,其结合于人p21启动子的区域,所述区域含有多拷贝共有序列的变异。p150 Sal 2也显示与具有类似元件的BAX启动子结合,并在凋亡刺激后激活其表达。这些结果表明p150 Sal 2与两个天然启动子的结合与体外定义的最佳结合序列相关的GC元件,其调节对于抑制肿瘤生长是重要的。
The product of the SALL2 protein p150Sal2 is a multi-zinc finger transcription factor with growth-arrest and pro-apoptotic functions that overlap those of p53. Its DNA binding properties are unknown. We have used a modified SELEX procedure with purified p150Sal2 and a pool of oligonucleotides of random sequence to identify those that are bound preferentially by p150Sal2. The consensus sequence for optimal binding in vitro is GGG(T/C)GGG, placing p150Sal2 among a large group of GC box-binding proteins including the Sp1 family of transcription factors. A triple zinc finger motif in p150Sal2 similar to that in Sp1 is required for DNA binding. p150Sal2 and Sp1 show evidence of co-operative binding in vitro and of interaction in vivo. p150Sal2, a known activator of the CDK inhibitor p21Cip1/Waf1 (p21), binds to regions of the human p21 promoter that contain variations of the consensus sequence in multiple copies. p150Sal2 is also shown to bind to the BAX promoter with similar elements and to activate its expression following an apoptotic stimulus. These results demonstrate binding of p150Sal2 to two natural promoters with GC elements related to the optimal binding sequence defined in vitro and whose regulation is important for suppression of tumor growth.
DOI: 10.1002/j.1460-2075.1988.tb02799.x
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