Novel brain specific bHLH transcription regulator, KW8

新型脑特异性 bHLH 转录调节因子 KW8

• 批准号: 09640819
• 负责人: MARUYAMA Kei
• 金额: $ 1.98万
• 依托单位: Tokyo Metropolitan Organization for Medical Research (1999)Okazaki National Research Institutes (1997-1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09640819/
• 关键词: KW8; Neuro D; Neuro D2; NDRF; bHLH; transcription; LTP; neuron-specific; 転写調節因子; 分化因子; NeuroD; KW8; basic helix-loop-helix; neuron; 差分; 転写調節

KW8, a NeuroD family basic helix-loop-helix protein, was cloned during the course of screening for the genes related to long term potentiation in rat hippocampal slice. It has a bHLH domain highly homologous with that of MATH-2 and NeuroD. On the other hand, the amino-acid sequence of the other regions had little homology with those of the known proteins. This protein consists of 381 amino acids and was detected only in neural tissue, indicating that it has an important role specific to neuronal activities. Its homologue NDRF/NeuroD was also reported. Its phosphorylation and spatiotemporal distribution was studied. KW8 was expressed only in brain tissues, such as the cerebral cortex, hippocampus and cerebellum. Immunohistological studies revealed that KW8 was localized in the nuclei of neurons. On immunoblotting of rat brain tissue, COS-1 cells and Neuro2A cells overexpressing KW8, this protein was detected as several diffuse bands. Alkaline phosphatase treatment reduced the molecular weights of these bands. Metabolic labeling with ィイD132ィエD1Pi in COS-1 cells confirmed that the KW8 protein was phosphorylated in vivo. Some of the physiological functions of KW8 might be regulated by this phosphorylation. In yeast, the GAL4 fusion protein containing the C-terminal region of KW8 activated transcription of the reporter gene, suggesting that KW8 had transcriptional activity.

KW8是一种基本的螺旋 - 环螺旋蛋白，在与大鼠邻使切片中的长期潜力相关的基因中被克隆了。仅在神经组织中检测到其他蛋白质的氨基酸序列，这表明其具有特定于神经元活性的重要作用。海马和脑脑研究中，KW8始终在神经元的核中局部在COS-1细胞中使用D132 YIR D1PI的标记证实，KW8蛋白在体内被磷酸化。

项目成果

Tomita T., Takikawa R., Koyama A., Morohashi Y., Takasugi N., Saido TC., Maruyama K., Iwatsubo T.: "C terminus of presenilin is required for overproduction of amyloidogenic Abeta 42 through stabilization and endoproteolysis of presenilin"J. Neurosci.. 19.

Tomita T.、Takikawa R.、Koyama A.、Morohashi Y.、Takasugi N.、Saido TC.、Maruyama K.、Iwatsubo T.：“早老素的 C 末端是通过稳定和内切蛋白水解过度产生淀粉样蛋白 Abeta 42 所必需的。

Shinozaki K, Kume H, Kuzume H,Obata K,Maruyama K: "Norbin, a neurite-outgrowth-related protein, is a cytosolic protein localized in somatodendritic region of neurons and distributed prominently in dendritic outgrowthing Purkinje cells"Mol. Brain Res.. 71.

Shinozaki K、Kume H、Kuzume H、Obata K、Maruyama K：“Norbin 是一种神经突生长相关蛋白，是一种位于神经元体树突区域的胞质蛋白，主要分布在树突生长浦肯野细胞中”Mol.

Asada H, Kawamura Y, Maruyama K, Kum H, Ding R-G, Kanbara N,Kuzume H,Sanbo M,Yagi T,Obata K: "Cleft palate and decreased brain g-aminobutyric acid in mice lacking the 67 kDA isoform of glutamic acid decarboxylase"Proc.Natl.Acad.Sci.USA. 94. 6496-6499 (199

Asada H、Kawamura Y、Maruyama K、Kum H、Ding R-G、Kanbara N、Kuzume H、Sanbo M、Yagi T、Obata K：“缺乏 67 kDA 谷氨酸亚型的小鼠出现腭裂和脑 g-氨基丁酸减少

Shinozaki K., Kume H., Obata K., Maruyama K.: "Norbin, a neurite-outgrowth-related protein, is a cytosolic protein localized in somatodendritic region of neurons and distributed prominently in dendritic out-growthing Purkinje cells"Mol. Brain Res.. 71. 36

Shinozaki K.、Kume H.、Obata K.、Maruyama K.：“Norbin 是一种神经突生长相关蛋白，是一种位于神经元体树突区域的胞质蛋白，主要分布在树突生长的浦肯野细胞中”Mol.

Shinozaki K, Maruyama K, Kume H, Kuzume H, Obata K: "A novel brain gene, Norbin, induced by treatment of tetraethylammonium in rat Hippocampal slice and accompanied with neurite-outgrowth in Neuro 2a cells."Biochem. Biophys. Res. Commun.. 240. 766-771 (19

Shinozaki K、Maruyama K、Kume H、Kuzume H、Obata K：“一种新的脑基因 Norbin，通过四乙铵处理大鼠海马切片诱导，并伴有 Neuro 2a 细胞中的神经突生长。”Biochem。