Functional analysis of glucocorticoid induced transcript 1(GLCCI1)

糖皮质激素诱导转录物1（GLCCI1）的功能分析

• 批准号: 21591398
• 负责人: YAN Kunimasa
• 金额: $ 3万
• 依托单位: Kyorin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591398/
• 关键词: 糖質ステロイド; Ｔ細胞; アポトーシス; Glcci1; Dlc8; PAK1; T細胞; 胸腺; 細胞内骨格; ステロイド; 精巣; 糸球体; ネフローゼ

The aim of the present study was to identify the protein function of GLCCI1, a novel gene induced by synthetic glucocorticoid. We found that GLCCI was a tubulin-associated phosphoprotein migrated at ～70 kDa that was induced via glucocorticoid-glucocorticoid receptor complex. We also found that both PAK1 anddynein-light chain 8 were the ligand proteins of GLCCI1, and that GLCCI1 interfered the PAK1 kinase activity against LC8 biogenesis, which led to T cell apoptosis. Our data suggested that the functional implication of GLCCI1 in PAK1-LC8 interaction might be a novel downstream cascade resembling synthetic glucocorticoid action as an immunosuppressant.

本研究的目的是鉴定合成糖皮质激素诱导的新基因GLCCI1的蛋白功能。我们发现GLCCI是一种由糖皮质激素-糖皮质激素受体复合体诱导的、大小约70 kDa的微管蛋白相关的磷酸蛋白。我们还发现，PAK1和动力蛋白轻链8都是GLCCI1的配基蛋白，GLCCI1干扰了PAK1的活性，抑制了LC8的生物发生，导致了T细胞的凋亡。我们的数据提示，GLCCI1在PAK1-LC8相互作用中的功能意义可能是一个新的下游级联，类似于合成的糖皮质激素作为免疫抑制剂的作用。