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Determination of a cleavage site of presenilin 2 protein in stably transfected SH-SY5Y human neuroblastoma cell lines.

作者信息

Shirotani K, Takahashi K, Ozawa K, Kunishita T, Tabira T

机构信息

Division of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.

出版信息

Biochem Biophys Res Commun. 1997 Nov 26;240(3):728-31. doi: 10.1006/bbrc.1997.7730.

DOI:10.1006/bbrc.1997.7730
PMID:9398634
Abstract

Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes are associated with early-onset autosomal dominant familial Alzheimer's disease, and the gene products are endoproteolytically processed to yield N-terminal fragments (NTF) and C-terminal fragments (CTF). We have studied the cleavage site of the PS2 protein in stably transfected human neuroblastoma cells. The 23 kD PS2-CTF was isolated by a combination of anion exchange chromatography and affinity chromatography and directly sequenced. The N-terminus of the PS2-CTF started at residue 307, which indicated that the cleavage occurs between Lys306 and Leu307 in the proximal portion of the large hydrophilic loop. This site is close to the cleavage positions observed in the PS1 protein.

摘要

相似文献

1
Determination of a cleavage site of presenilin 2 protein in stably transfected SH-SY5Y human neuroblastoma cell lines.
Biochem Biophys Res Commun. 1997 Nov 26;240(3):728-31. doi: 10.1006/bbrc.1997.7730.
2
Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue.早老素蛋白在苏氨酸291和丙氨酸299之间经历异质性内切蛋白水解,并以稳定的N端和C端片段形式存在于正常和阿尔茨海默病脑组织中。
Neurobiol Dis. 1997;3(4):325-37. doi: 10.1006/nbdi.1997.0129.
3
Presenilin 2 expression in neuronal cells: induction during differentiation of embryonic carcinoma cells.
Exp Cell Res. 2000 Mar 15;255(2):192-206. doi: 10.1006/excr.1999.4791.
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Proteolytic fragments of the Alzheimer's disease associated presenilins-1 and -2 are phosphorylated in vivo by distinct cellular mechanisms.阿尔茨海默病相关早老素-1和-2的蛋白水解片段在体内通过不同的细胞机制发生磷酸化。
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5
Mapping the APP/presenilin (PS) binding domains: the hydrophilic N-terminus of PS2 is sufficient for interaction with APP and can displace APP/PS1 interaction.绘制淀粉样前体蛋白(APP)/早老素(PS)结合结构域:PS2的亲水性N末端足以与APP相互作用,并可取代APP/PS1的相互作用。
Neurobiol Dis. 1999 Feb;6(1):43-55. doi: 10.1006/nbdi.1998.0212.
6
Stable association of presenilin derivatives and absence of presenilin interactions with APP.早老素衍生物的稳定结合以及早老素与淀粉样前体蛋白(APP)之间不存在相互作用。
Neurobiol Dis. 1998 Apr;4(6):438-53. doi: 10.1006/nbdi.1998.0171.
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Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios.早老素2家族性阿尔茨海默病突变导致功能部分丧失以及β淀粉样蛋白42/40比率发生显著变化。
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8
gamma-Secretase complexes containing N- and C-terminal fragments of different presenilin origin retain normal gamma-secretase activity.包含不同早老素来源的N端和C端片段的γ-分泌酶复合物保持正常的γ-分泌酶活性。
J Neurochem. 2005 Nov;95(3):880-90. doi: 10.1111/j.1471-4159.2005.03415.x. Epub 2005 Aug 31.
9
Presenilin-1 protein expression in familial and sporadic Alzheimer's disease.早老素-1蛋白在家族性和散发性阿尔茨海默病中的表达
Ann Neurol. 1997 Jun;41(6):742-53. doi: 10.1002/ana.410410610.
10
Presenilin 1 regulates the processing of beta-amyloid precursor protein C-terminal fragments and the generation of amyloid beta-protein in endoplasmic reticulum and Golgi.早老素1在内质网和高尔基体中调节β-淀粉样前体蛋白C末端片段的加工以及β-淀粉样蛋白的生成。
Biochemistry. 1998 Nov 24;37(47):16465-71. doi: 10.1021/bi9816195.

引用本文的文献

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2
Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis.早老素内切酶水解的三个氨基酸间隔提示 γ-分泌酶介导的跨膜蛋白酶解的一种普遍的逐步裂解。
J Neurosci. 2010 Jun 9;30(23):7853-62. doi: 10.1523/JNEUROSCI.1443-10.2010.
3
Affinity pulldown of γ-secretase and associated proteins from human and rat brain.
从人和鼠脑中亲和拉下γ-分泌酶及其相关蛋白。
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Characterization of APH-1 mutants with a disrupted transmembrane GxxxG motif.具有跨膜GxxxG基序破坏的APH-1突变体的表征。
J Mol Neurosci. 2006;29(1):35-43. doi: 10.1385/JMN:29:1:35.
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Metabolism of presenilins.早老素的代谢
J Mol Neurosci. 2001 Oct;17(2):183-92. doi: 10.1385/JMN:17:2:183.
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Neuroinflammatory signaling upregulation in Alzheimer's disease.阿尔茨海默病中神经炎症信号上调
Neurochem Res. 2000 Oct;25(9-10):1173-84. doi: 10.1023/a:1007627725251.
7
Presenilins: structural aspects and posttranslational events.早老素:结构方面及翻译后事件
Mol Neurobiol. 1999 Jun;19(3):255-65. doi: 10.1007/BF02821716.
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C-terminal maturation fragments of presenilin 1 and 2 control secretion of APP alpha and A beta by human cells and are degraded by proteasome.早老素1和2的C末端成熟片段控制人细胞中APPα和Aβ的分泌,并被蛋白酶体降解。
Mol Med. 1999 Mar;5(3):160-8.
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Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis.早老素-2的磷酸化作用可调节其被半胱天冬酶的切割,并延缓细胞凋亡进程。
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1391-6. doi: 10.1073/pnas.96.4.1391.