Analysis of the Ro52's function and structure and biological significance of autoimmune disease

Ro52的功能结构分析及自身免疫性疾病的生物学意义

• 批准号: 18591100
• 负责人: YAMOCHI Tadanori
• 金额: $ 2.57万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591100/
• 关键词: Ro52; Sjogren's syndrome; Autoimmune Disease; Sjogren'S syndrome

An autoantibody against SS-A/Ro52 (Ro52) is most frequently found in the sera of patients with Sjogren's syndrome and systemiclupus erythematosus,. However, the physiological function of the autoantigen SS-A/Ro52 has not yet been elucidated. To investigate this function, we have studied the role of Ro52 protein in T cell activation.Then, we found that overexpression of SS-A/Ro52 in Jurkat T cell resulted in enhanced IL-2 production following CD28 stimulation. Moreover to investigate the mechanism of Ro52 signaling pathway, we searched Ro52 associated molecules. And, we identified human decapping enzyme 2 (hDCP2) as a binding protein with Ro52. Ro52 colocalized with hDCP2 in processing bodies (p-bodies) in 293 FT cells. We also demonstrated that the N-terminus and C-terminus of Ro52 bound to hDCP2 in a mammalian GST pull down assay system. Moreover, in vitro decapping assay revealed that Ro52 enhanced decapping activity of hDCP2, as well as upregulating hDCP2 expression. Our present data support the novel notion of the association between Ro52 with hDCP2 protein in cytoplasmic p-bodies, playing a role in mRNA metabolism in response to cellular stimulation.

抗SS-A/Ro 52（Ro 52）的自身抗体最常见于干燥综合征和系统性红斑狼疮患者的血清中。然而，自身抗原SS-A/Ro 52的生理功能尚未阐明。为了研究Ro 52蛋白在T细胞活化中的作用，我们发现过表达SS-A/Ro 52的Jurkat T细胞在CD 28刺激下IL-2的产生增加。为了进一步研究Ro 52信号通路的作用机制，我们还寻找了Ro 52的相关分子。并且，我们鉴定了人脱帽酶2（hDCP 2）作为Ro 52的结合蛋白。Ro 52与hDCP 2共定位在293个FT细胞中的加工体（p体）中。我们还证明了在哺乳动物GST下拉测定系统中Ro 52的N-末端和C-末端与hDCP 2结合。此外，体外脱帽实验表明Ro 52增强hDCP 2的脱帽活性，以及上调hDCP 2的表达。我们目前的数据支持Ro 52与细胞质p体中hDCP 2蛋白之间的关联的新概念，在响应细胞刺激的mRNA代谢中发挥作用。

项目成果

T-cell activation via CD26 and caveolin-1 in rheumatoid synovium.

• DOI: 10.1007/s10165-005-0452-4
• 发表时间: 2006
• 期刊: Modern rheumatology
• 影响因子: 2.2

Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors

• DOI: 10.1158/1078-0432.ccr-07-0110
• 发表时间: 2007-07-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Inamoto, Teruo;Yamada, Taketo;Morimoto, Chikao
• 通讯作者: Morimoto, Chikao

Hypermethylation of CpG islands in p16 as a prognostic factor for diffuse large B-cell lymphoma in a high-risk group.

• DOI: 10.1016/j.leukres.2005.11.004
• 发表时间: 2006-07
• 期刊: Leukemia research
• 影响因子: 2.7
• 作者: E. Shiozawa;M. Takimoto;R. Makino;D. Adachi;B. Saito;Toshiko Yamochi‐Onizuka;T. Yamochi;Junko Shimozuma;Takashi Maeda;Y. Kohno;K. Kawakami;T. Nakamaki;S. Tomoyasu;A. Shiokawa;H. Ota

Anti-CD26 monoclonal antibody-mediated G1-S arrest of human renal clear cell carcinoma Caki-2 is associated with retinoblastoma substrate dephosphorylation, cychn-dependent kinase 2 reduction, p27(kip1) enhancement, and disruption of binding to the extrac

抗 CD26 单克隆抗体介导的人肾透明细胞癌 Caki-2 的 G1-S 期阻滞与视网膜母细胞瘤底物去磷酸化、cychn 依赖性激酶 2 减少、p27(kip1) 增强以及与提取物结合的破坏有关

• 发表时间: 2007
• 期刊: Clinical Cancer Research 12
• 作者: 大沼 圭;稲元輝夫;Teruo Inamoto;Kei Ohnuma;Teruo Inamoto
• 通讯作者: Teruo Inamoto

Anti-CD26 monoclonal antibody-mediated G1-S arrest of human renal clear cell carcinoma Caki-2 is associated with retinoblastoma substrate dephosphorylation, cyclin-dependent kinase 2 reduction, P27(kip1)enhancement, and disruption of binding to the extrac

抗 CD26 单克隆抗体介导的人肾透明细胞癌 Caki-2 的 G1-S 期阻滞与视网膜母细胞瘤底物去磷酸化、细胞周期蛋白依赖性激酶 2 减少、P27(kip1) 增强以及与提取物结合的破坏有关

• 发表时间: 2006
• 期刊: Clinical Cancer Research 12
• 作者: 大沼 圭;稲元輝夫;Teruo Inamoto;Kei Ohnuma;Teruo Inamoto;大沼 圭;稲元輝夫
• 通讯作者: 稲元輝夫