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Functional Analysis of the human CTLH complex, Homolog of Yeast GID complex, in Muscle Cells

肌肉细胞中人类 CTLH 复合物（酵母 GID 复合物的同源物）的功能分析

基本信息

批准号：
17590944
负责人：
UEDA Atsuhisa
金额：
$ 2.18万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590944/
关键词：
GID complex ARMC8 p44 CTLH p48 EMLP RanBPM CTLHドメイングルコース効果プロテオリシス

项目摘要

Ran binding protein in microtubule organising centre (RanBPM) was originally isolated as a protein that binds to the small GTPase Ran. RanBPM also associates with the HGF receptor MET, p75 the neurotrophin receptor, and integrin LFA-1, and modifies the signaling of some of these molecules. Therefore, RanBPM may function as a scaffolding protein that coordinates the signaling input of cell surface receptors with intracellular signaling pathways. Previously, we identified RanBPM as a component of a 20S large protein complex. Here we purified the complex from soluble extract of HEK293 cells by an antibody against RanBPM, and identified Muskelin, ARMC8α, p48EMLP, ARMC8β, and p44CTLH as complex components by tandem mass spectrometry. ARMC8α and ARMC8βare novel armadillo-repeat proteins. Since the N-terminal 364 amino acids of ARMC8a and ARMC8βwere completely conserved, these proteins are probably alternatively spliced products from the same gene. Interestingly, RanBPM, Muskelin, p48EMLP, and p44CTLH possess LisH/ CTLH motifs, which are present in proteins involved in microtubule dynamics, cell migration, nucleokinesis, and chromosome segregation. Immunoblot analysis showed dominant expression of ARMC8α, ARMC8β, p48EMLP, and p44CTLH mRNAs in skeletal muscle and testis. We next confirmed the in vivo association of each complex component by co-immunoprecipitation assays using the Cos-7 cells in which these components were exogenously overexpressed. Pull-down assay using bacterially-expressed Twa1 revealed that each In vitro-translated component could bind to the Twa1. Finally, we confirmed the cellular co-localization of these proteins. Taken together, we revealed that RanBPM, Muskelin, p48EMLP, Twa1, p44CTLH, and ARMC8 form complexes in cells.

微管组织中心的Ran结合蛋白（RanBPM）最初是作为一种与小的GTdR Ran结合的蛋白质分离出来的。RanBPM还与HGF受体MET、神经营养因子受体p75和整联蛋白LFA-1相关，并改变这些分子中的一些分子的信号传导。因此，RanBPM可能作为一种支架蛋白，协调细胞表面受体的信号输入与细胞内信号通路。以前，我们确定RanBPM作为一个组成部分的20 S大蛋白质复合物。在此，我们通过RanBPM抗体从HEK 293细胞的可溶性提取物中纯化了复合物，并通过串联质谱法鉴定了Muskelin、ARMC 8 α、p48 EMLP、ARMC 8 β和p44 CTLH为复合物组分。ARMC 8 α和ARMC 8 β是新的犰狳重复序列蛋白。由于ARMC 8a和ARMC 8 β的N-末端364个氨基酸完全保守，这些蛋白可能是来自同一基因的选择性剪接产物。有趣的是，RanBPM，Muskelin，p48 EMLP和p44 CTLH具有LisH/ CTLH基序，这些基序存在于参与微管动力学，细胞迁移，核分裂和染色体分离的蛋白质中。免疫印迹分析显示ARMC 8 α、ARMC 8 β、p48 EMLP和p44 CTLH mRNA在骨骼肌和睾丸中呈优势表达。接下来，我们通过使用Cos-7细胞的共免疫沉淀试验证实了每种复合物组分的体内缔合，其中这些组分是外源性过表达的。使用细菌表达的Twa 1的下拉测定显示，每个体外翻译的组分可以结合Twa 1。最后，我们证实了这些蛋白质的细胞共定位。综上所述，我们发现RanBPM，Muskelin，p48 EMLP，Twa 1，p44 CTLH和ARMC 8在细胞中形成复合物。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lungs attenuates elastase-induced pulmonary emphysema in mice.

DOI：
10.1089/hum.2005.16.318
发表时间：
2005-04
期刊：
Human gene therapy
影响因子：
4.2
作者：
T. Shinohara;T. Kaneko;Y. Nagashima;A. Ueda;A. Tagawa;Y. Ishigatsubo
通讯作者：
T. Shinohara;T. Kaneko;Y. Nagashima;A. Ueda;A. Tagawa;Y. Ishigatsubo

Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritis

DOI：
10.1002/art.21754
发表时间：
2006-04-01
期刊：
ARTHRITIS AND RHEUMATISM
影响因子：
0
作者：
Kobayashi, H;Takeno, M;Ishigatsubo, Y
通讯作者：
Ishigatsubo, Y

Heme oxygenase-1 inhibits cigarette smoke-induced increase in the tracheal mucosal permeabilty in guinea pigs in vivo.

血红素加氧酶-1 抑制香烟烟雾引起的豚鼠体内气管粘膜通透性增加。

DOI：
发表时间：
2005
期刊：
Inflamm Res, 54(5)
影响因子：
0
作者：
Tagawa A;Ueda_A;et al.
通讯作者：
et al.

Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: use in the differential diagnosis of hyperferritinemia.

血清HO-1在嗜血型综合征和成人疾病中的血清HO-1疾病：用于高铁蛋白血症的鉴别诊断。

DOI：
10.1186/ar1721
发表时间：
2005
期刊：
ARTHRITIS RESEARCH & THERAPY
影响因子：
4.9
作者：
Kirino, Yohei;Takeno, Mitsuhiro;Iwasaki, Mika;Ueda, Atsuhisa;Ohno, Shigeru;Shirai, Akira;Kanamori, Heiwa;Tanaka, Katsuaki;Ishigatsubo, Yoshiaki
通讯作者：
Ishigatsubo, Yoshiaki

Tumor Necrosis Factor α Acceleration of Inflammatory Responses by Down-Regulation Heme Oxygenase 1 in Human Peripheral Monocytes

肿瘤坏死因子 α 通过下调人外周单核细胞血红素加氧酶 1 加速炎症反应