TIP49, homologous to the bacterial DNA helicase RuvB, acts as an autoantigen in human

TIP49, homologous to the bacterial DNA helicase RuvB, acts as an autoantigen in human
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DOI:
10.1006/bbrc.1998.8504
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发表时间:
1998-04-28
影响因子:
3.1
通讯作者:
Tamura, T
Tamura, T
中科院分区:
生物学4区
文献类型:
--
作者:
Makino, Y;Mimori, T;Tamura, T

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TATA结合蛋白(TBP)是转录调控的核心成分,与多种转录调控因子形成复合物。我们已经分离出一个新的人cDNA的49 kD TBP相互作用蛋白(TIP 49)。人TIP 49与细菌RuvB蛋白高度同源,RuvB蛋白作为DNA解旋酶起作用以促进霍利迪连接的分支迁移。用抗TIP 49抗体进行的免疫荧光分析显示了典型的点状核染色模式,表明TIP 49包含在核内的大分子结构中,并可能参与核事件,如转录和重组。此外,甘油梯度分析表明,TIP 49存在于核提取物中的大分子复合物中。有趣的是,我们在自身免疫性疾病如多发性肌炎/皮肌炎和自身免疫性肝炎患者的血清中检测到高水平的抗TIP 49的自身抗体。这表明针对该蛋白的自身抗体是特定结缔组织疾病的新标志物。这些发现提供了进一步的证据,表明上述大分子结构是由自身免疫机制靶向的。抗TIP 49抗体可作为临床诊断和研究核内结构的有用探针。(C)北京:科学出版社.
TATA-binding protein (TBP), a central component for transcriptional regulation, forms complexes with various transcription regulators. We have isolated a novel human cDNA for a 49-kD TBP-interacting protein (TIP49). The human TIP49 was highly homologous to bacterial RuvB proteins that function as a DNA helicase to promote branch migration of the Holliday junction. Immunofluorescence analysis using anti-TIP49 antibody showed a typical dot-shaped nuclear staining pattern, suggesting that TIP49 is included in a macromolecular structure in the nucleus and may participate in nuclear events such as transcription and recombination. Moreover, glycerol gradient analysis demonstrated that TIP49 is present in a macromolecular complex in nuclear extracts. Interestingly, we detected a high level of autoantibodies against TIP49 in sera of patients with autoimmune diseases such as polymyositis/dermatomyositis and autoimmune hepatitis. This indicates that the autoantibody against this protein is a new marker for particular connective tissue diseases. These findings provide further evidence that the macromolecular structures described above are targeted by an autoimmune mechanism. The anti-TIP49 antibodies can be useful probes for clinical diagnosis and for investigation of intranuclear structure. (C) 1998 Academic Press.