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首页> 外文期刊>Biochemistry >High-Affinity Binding of Tumor-Suppressor Protein p53 and HMGB1 to Hemicatenated DNA Loops
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High-Affinity Binding of Tumor-Suppressor Protein p53 and HMGB1 to Hemicatenated DNA Loops

机译：肿瘤抑制蛋白P53和HMGB1至半丙烯酸二氧化碳环的高亲和力结合

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摘要

We have recently observed that chromatin architectural protein HMGB1 (previously reported to be involved in numerous biological processes such as DNA replication,recombination,repair,tumor growth,and metastasis) could bind with extremely high affinity (K_d< 1 pM) to a novel DNA structure that forms a DNA loop maintained at its base by a hemicatenane (hcDNA).The loop of hcDNA contains a track of repetitive sequences derived from CA-microsatellites.Here,we report using a gel-retardation assay that tumor-suppressor protein p53 can also bind to hcDNA.p53 is a crucial molecule protecting cells from malignant transformation by regulating cell-cycle progression,apoptosis,and DNA repair by activation or repression of transcription of its target genes by binding to specific p53 DNA-binding sites and/or certain types of DNA lesions or alternative DNA structures.The affinity of p53 for hcDNA (containing sequences with no resemblance to the p53 DNA consensus sequence) is >40-fold higher (K_d approx 0.5 nM) than that for its natural specific binding sites within its target genes (Mdm2 promoter).Binding of p53 to hcDNA remains detectable in the presence of up to approx 4 orders of magnitude of mass excess of competitor linear DNA,suggesting a high specificity of the interaction.p53 displays a higher affinity for hcDNA than for DNA minicircles (lacking functional p53-specific binding sequence) with a size similar to that of the loop within the hcDNA,indicating that the extreme affinity of p53 for hcDNA is likely due to the binding of the protein to the hemicatenane.Although binding of p53 to hcDNA occurs in the absence of the nonspecific DNA-binding extreme carboxy-terminal regulatory domain (30-C,residues 363-393),the isolated 30-C domain (but not the sequence-specific p53 "core domain",residues 94- 312) can also bind hcDNA.Only the full-length p53 can form stable ternary complexes with hcDNA and HMGB1.The possible biological relevance of p53 and HMGB1 binding to hemicatenanes is discussed.
机译：我们最近观察到染色质架构蛋白HMGB1（先前据报道涉及DNA复制，重组，修复，肿瘤生长和转移等众多生物学过程）可以与新的DNA极高亲和力（K_D <1 PM）结合形成在其基碱（HCDNA）处保持的DNA环的结构。HCDNA的环含有衍生自Ca-microsatellites的重复序列的轨道。：NE，我们使用凝胶延迟测定报告肿瘤抑制蛋白P53可以还结合HCDNA.p53是通过通过与特异性P53 DNA结合位点结合和/或某些方法来调节细胞周期进展，细胞凋亡和DNA修复来保护来自恶性转化的细胞免受恶性转化的关键分子。通过结合特异性p53 DNA结合位点和/或某些DNA病变或替代DNA结构的类型。P53对HCDNA的亲和力（含有与P53 DNA共有序列的相似性的序列）高出40倍（K_D Appro ×0.5nm）比其靶基因内的天然特异性结合位点（MDM2启动子）内的天然特异性结合位点。在竞争对手线性DNA的高达约4个质量级的存在下，P53对HCDNA进行仍然可检测到，表明高度相互作用的特异性。P53对HCDNA的亲和力显示比对于DNA小碱基（缺乏功能性P53特异性结合序列），其尺寸与HCDNA内的环的尺寸类似，表明P53对于HCDNA的极端亲和力可能是由于蛋白质与半丙酮的结合。虽然在没有非特异性DNA结合的极端羧基末端调节结构域（30-C，残基363-393）的不存在下，虽然P53与HCDNA的结合发生，但是分离的30-C域（但不是序列特异性P53“核心结构域”，残留物94-312）也可以结合HCDNA.Only全长P53可以形成具有HCDNA和HMGB1的稳定的三元复合物。P53和HMGB1与半丙烯酸盐结合的可能生物学相关性讨论。

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  • 来源
    《Biochemistry》 |2004年第22期|共11页
  • 作者

    Michal Stros; Eva Muselikova-Polanska; Sarka Pospisilova;

  • 作者单位

    Laboratory of Analysis of Chromosomal Proteins Academy of Sciences of the Czech Republic Institute of Biophysics 612 65 Brno Czech Republic Institut Jacques Monod 75251 Paris 05 France and Center of Molecular Biology and Gene Therapy Department of In;

    Laboratory of Analysis of Chromosomal Proteins Academy of Sciences of the Czech Republic Institute of Biophysics 612 65 Brno Czech Republic Institut Jacques Monod 75251 Paris 05 France and Center of Molecular Biology and Gene Therapy Department of In;

    Laboratory of Analysis of Chromosomal Proteins Academy of Sciences of the Czech Republic Institute of Biophysics 612 65 Brno Czech Republic Institut Jacques Monod 75251 Paris 05 France and Center of Molecular Biology and Gene Therapy Department of In;

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  • 正文语种 eng
  • 中图分类 生物化学;
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