Initial description of the human NLRP3 promoter.
Initial description of the human NLRP3 promoter.
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DOI：
10.1038/gene.2008.66
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发表时间：
2008-12
影响因子：
5
通讯作者：
Hoffman, H. M.
中科院分区：
文献类型：
--
作者：
Anderson, J. P.;Mueller, J. L.;Misaghi, A.;Anderson, S.;Sivagnanam, M.;Kolodner, R. D.;Hoffman, H. M.
NLRP 3（CIAS 1）中的突变在一系列相关的炎症性疾病中被鉴定，这些炎症性疾病被称为cryopyrin病，因为NLRP 3编码蛋白cryopyrin。大约40%的典型表现的患者缺乏NLRP 3编码区的突变，这表明异质性或表观遗传因素。Cryopyrin是促炎细胞因子释放的关键调节剂。因此，NLRP 3启动子序列的变异可能对cryopyrin病和其他炎性疾病患者的疾病状态有影响。在这篇报道中，我们证实了三种5′-非翻译区剪接形式，具有两个独立的转录起始位点，并确定了潜在的启动子区域和六个新的DNA启动子变体。一种变体对于突变阴性的cryopyrinopathy患者是独特的，并且增加体外基因表达。现在可以进行更多的研究来进一步表征NLRP 3启动子和序列变体，这将导致更好地理解NLRP 3表达的调控及其在疾病中的作用。
Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory disorders, known as cryopyrinopathies since NLRP3 codes for the protein cryopyrin. Approximately 40% of patients with classic presentation lack mutations in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors. Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore, variations in the NLRP3 promoter sequence may have effects on disease state in patients with cryopyrinopathies and other inflammatory diseases. In this report, we confirmed three 5′-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. One variant is unique to a mutation negative cryopyrinopathy patient and increases in vitro gene expression. Additional studies can now be performed to further characterize the NLRP3 promoter and sequence variants, which will lead to better understanding of the regulation of NLRP3 expression and its role in disease.
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