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

被引：34

作者：

Shirotani, K ^{[1
]}

Takahashi, K ^{[1
]}

Ozawa, K ^{[1
]}

Kunishita, T ^{[1
]}

Tabira, T ^{[1
]}

机构：

[1] NATL CTR NEUROL & PSYCHIAT,NATL INST NEUROSCI,DIV DEMYELINATING DIS & AGING,KODAIRA,TOKYO 187,JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1997年 / 240卷 / 03期

基金：

日本科学技术振兴机构;

关键词：

D O I：

10.1006/bbrc.1997.7730

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Lys(306) and Leu(307) in the proximal portion of the large hydrophilic loop. This site is close to the cleavage positions observed in the PS1 protein. (C) 1997 Academic Press.

引用

页码：728 / 731

页数：4

共 15 条

[1] Familial Alzheimer's disease-linked presenilin 1 variants elevate A beta 1-42/1-40 ratio in vitro and in vivo [J].

Borchelt, DR ;

Thinakaran, G ;

Eckman, CB ;

Lee, MK ;

Davenport, F ;

Ratovitsky, T ;

Prada, CM ;

Kim, G ;

Seekins, S ;

Yager, D ;

Slunt, HH ;

Wang, R ;

Seeger, M ;

Levey, AI ;

Gandy, SE ;

Copeland, NG ;

Jenkins, NA ;

Price, DL ;

Younkin, SG .

NEURON, 1996, 17 (05) :1005-1013

[2] Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice [J].

Citron, M ;

Westaway, D ;

Xia, WM ;

Carlson, G ;

Diehl, T ;

Levesque, G ;

JohnsonWood, K ;

Lee, M ;

Seubert, P ;

Davis, A ;

Kholodenko, D ;

Motter, R ;

Sherrington, R ;

Perry, B ;

Yao, H ;

Strome, R ;

Lieberburg, I ;

Rommens, J ;

Kim, S ;

Schenk, D ;

Fraser, P ;

Hyslop, PS ;

Selkoe, DJ .

NATURE MEDICINE, 1997, 3 (01) :67-72

[3] Increased amyloid-beta 42(43) in brains of mice expressing mutant presenilin 1 [J].

Duff, K ;

Eckman, C ;

Zehr, C ;

Yu, X ;

Prada, CM ;

Pereztur, J ;

Hutton, M ;

Buee, L ;

Harigaya, Y ;

Yager, D ;

Morgan, D ;

Gordon, MN ;

Holcomb, L ;

Refolo, L ;

Zenk, B ;

Hardy, J ;

Younkin, S .

NATURE, 1996, 383 (6602) :710-713

[4]

Kim TW, 1997, J BIOL CHEM, V272, P11006

[5] Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease [J].

Kim, TW ;

Pettingell, WH ;

Jung, YK ;

Kovacs, DM ;

Tanzi, RE .

SCIENCE, 1997, 277 (5324) :373-376

[6] FACILITATION OF LIN-12-MEDIATED SIGNALING BY SEL-12, A CAENORHABDITIS-ELEGANS S182 ALZHEIMERS-DISEASE GENE [J].

LEVITAN, D ;

GREENWALD, I .

NATURE, 1995, 377 (6547) :351-354

[7] CANDIDATE GENE FOR THE CHROMOSOME-1 FAMILIAL ALZHEIMERS-DISEASE LOCUS [J].

LEVYLAHAD, E ;

WASCO, W ;

POORKAJ, P ;

ROMANO, DM ;

OSHIMA, J ;

PETTINGELL, WH ;

YU, CE ;

JONDRO, PD ;

SCHMIDT, SD ;

WANG, K ;

CROWLEY, AC ;

FU, YH ;

GUENETTE, SY ;

GALAS, D ;

NEMENS, E ;

WIJSMAN, EM ;

BIRD, TD ;

SCHELLENBERG, GD ;

TANZI, RE .

SCIENCE, 1995, 269 (5226) :973-977

[8] Presenilins are processed by caspase-type proteases [J].

Loetscher, H ;

Deuschle, U ;

Brockhaus, M ;

Reinhardt, D ;

Nelboeck, P ;

Mous, J ;

Grunberg, J ;

Haass, C ;

Jacobsen, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20655-20659

[9] Presenilin proteins undergo heterogeneous endoproteolysis between Thr(291) and Ala(299) and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue [J].

Podlisny, MB ;

Citron, M ;

Amarante, P ;

Sherrington, R ;

Xia, WM ;

Zhang, JM ;

Diehl, T ;

Levesque, G ;

Fraser, P ;

Haass, C ;

Koo, EHM ;

Seubert, P ;

StGeorgeHyslop, P ;

Teplow, DB ;

Selkoe, DJ .

NEUROBIOLOGY OF DISEASE, 1997, 3 (04) :325-337

[10] FAMILIAL ALZHEIMERS-DISEASE IN KINDREDS WITH MISSENSE MUTATIONS IN A GENE ON CHROMOSOME-1 RELATED TO THE ALZHEIMERS-DISEASE TYPE-3 GENE [J].

ROGAEV, EI ;

SHERRINGTON, R ;

ROGAEVA, EA ;

LEVESQUE, G ;

IKEDA, M ;

LIANG, Y ;

CHI, H ;

LIN, C ;

HOLMAN, K ;

TSUDA, T ;

MAR, L ;

SORBI, S ;

NACMIAS, B ;

PIACENTINI, S ;

AMADUCCI, L ;

CHUMAKOV, I ;

COHEN, D ;

LANNFELT, L ;

FRASER, PE ;

ROMMENS, JM ;

STGEORGEHYSLOP, PH .

NATURE, 1995, 376 (6543) :775-778

← 1 2 →