Specificity from nonspecific interaction: regulation of tumor necrosis factor- activity by DNA
Specificity from nonspecific interaction: regulation of tumor necrosis factor- activity by DNA
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DOI：
10.1074/jbc.ra119.007586
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发表时间：
2019-04-19
影响因子：
4.8
通讯作者：
Zhang, Yixin
中科院分区：
文献类型：
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作者：
Andrade, Helena;Lin, Weilin;Zhang, Yixin
作为阴离子生物聚合物，寡核苷酸可以具有独立于其作为遗传信息的存储和流动的介质的作用的生物学功能。在本文中，我们研究了DNA和促炎细胞因子肿瘤坏死因子（TNF）之间的相互作用。尽管各种形式的DNA以低的解离常数m与TNF结合，但这种相互作用稳定了TNF的三聚体形式并增强了其细胞毒性作用。基于这一机制，设计了一种光开关TNF（TNF-2-nitrovanryloxycarbonyl），其对DNA介导的TNF活性上调的敏感性可以通过光照射来调节。在这项研究中描述的机制代表了一个通用的模型，以了解参与非特异性相互作用的生物分子在调节其生物功能。由于这种相互作用不是DNA序列特异性的，因此通常应考虑基于阿托伐他汀的治疗方法产生的效果。
As anionic biopolymers, oligonucleotides can have biological functions independent from their roles as the medium for the storage and flow of genetic information. In this paper, we investigated the interaction between DNA and the pro-inflammatory cytokine tumor necrosis factor- (TNF). Although various forms of DNA bind to TNF with low m dissociation constants, the interaction stabilizes the trimeric form of TNF and enhances its cytotoxic effect. Based on this mechanism, a photoswitchable TNF (TNF-2-nitroveratryloxycarbonyl) has been designed whose sensitivity to DNA-mediated up-regulation of TNF activity can be tuned by light irradiation. The mechanism described in this study represents a general model to understand the involvement of nonspecific interactions among biomolecules in regulating their biological functions. Because the interaction is not DNA sequence-specific, the resulting effect should be considered for oligonucleotide-based therapeutics in general.