Mutant p53 proteins bind DNA in a DNA structure-selective mode.
Mutant p53 proteins bind DNA in a DNA structure-selective mode.
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DOI：
10.1093/nar/gki252
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发表时间：
2005
影响因子：
14.9
通讯作者：
Deppert W
中科院分区：
文献类型：
--
作者：
Göhler T;Jäger S;Warnecke G;Yasuda H;Kim E;Deppert W
尽管失去了序列特异性DNA结合，突变型p53（mutp53）蛋白可以诱导或抑制mutp53特异性靶基因的转录。迄今为止，mutp53转录调控的分子基础尚不清楚，但越来越多的证据表明mutp53与DNA的特异性相互作用可能发挥重要作用。到目前为止，mutp53 DNA结合的共同特征的缺乏，即共同序列元件的存在，阻碍了mutp53 DNA结合的进一步表征。从我们以前的发现，DNA结构是一个重要的决定因素野生型p53（wtp53）DNA结合，我们分析了各种mutp53蛋白的结合寡核苷酸模仿非B DNA结构。使用各种DNA结合试验，我们表明mutp53蛋白选择性且高亲和力地与非B DNA结合。与wtp53的序列特异性和DNA结构依赖性结合相反，mutp53 DNA与非B DNA的结合仅依赖于DNA的立体特异性构型，而不依赖于DNA序列。我们建议，mutp53蛋白的DNA结构选择性结合是mutp53与MAR元件的相互作用和mutp53介导的转录活性的基础。
Despite the loss of sequence-specific DNA binding, mutant p53 (mutp53) proteins can induce or repress transcription of mutp53-specific target genes. To date, the molecular basis for transcriptional modulation by mutp53 is not understood, but increasing evidence points to the possibility that specific interactions of mutp53 with DNA play an important role. So far, the lack of a common denominator for mutp53 DNA binding, i.e. the existence of common sequence elements, has hampered further characterization of mutp53 DNA binding. Emanating from our previous discovery that DNA structure is an important determinant of wild-type p53 (wtp53) DNA binding, we analyzed the binding of various mutp53 proteins to oligonucleotides mimicking non-B DNA structures. Using various DNA-binding assays we show that mutp53 proteins bind selectively and with high affinity to non-B DNA. In contrast to sequence-specific and DNA structure-dependent binding of wtp53, mutp53 DNA binding to non-B DNA is solely dependent on the stereo-specific configuration of the DNA, and not on DNA sequence. We propose that DNA structure-selective binding of mutp53 proteins is the basis for the well-documented interaction of mutp53 with MAR elements and for transcriptional activities mediates by mutp53.
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影响因子：
4.8
作者：
Friedler, A;Veprintsev, DB;Fersht, AR
通讯作者：
Fersht, AR
影响因子：
14.9
作者：
BAKALKIN, G;SELIVANOVA, G;WIMAN, KG
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DOI：
10.1073/pnas.91.1.413
发表时间：
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影响因子：
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作者：
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DOI：
10.1006/bbrc.2000.3965
发表时间：
2000-12-20
影响因子：
3.1
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影响因子：
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作者：
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