23 295

Cited 155 times in

Proapoptotic effects of tau cleavage product generated by caspase-3.

Chung, CW; Song, YH; Kim, IK; Yoon, WJ; Ryu, BR; Jo, DG; Woo, HN; Kwon, YK; Kim, HH; Gwag, BJ; Mook-Jung, IH; Jung, YK
Neurobiology of disease, 8(1):162-172, 2001
Journal Title
Neurobiology of disease
Using an in vitro translation assay to screen a human brain cDNA library, we isolated the microtubule-associated protein Tau and determined it to be a caspase-3 substrate whose C-terminal cleavage occurred during neuronal apoptosis. DeltaTau, the 50-kDa cleavage product, was detected by Western blot in apoptotic cortical cells probed with anti-PHF-1 and anti-Tau-5 antibodies, but not anti-T-46 antibody which recognizes the C-terminus. Overexpression of DeltaTau in SK-N-BE2(C) cells significantly increased the incidence of cell death. Staurosporine-induced Tau cleavage was blocked by 20 microM z-Asp-Glu-Val-Asp-chloromethylketone, a caspase-3 inhibitor, and in vitro, Tau was selectively cleaved by caspase-3 or calpain, a calcium-activated protease, but not by caspases-1, -8, or -9. (D421E)-Tau, a mutant in which Asp421 was replaced with a Glu, was resistant to cleavage by caspase-3 and tended to suppress staurosporine-induced cell death more efficiently than did wild-type Tau in both transient and stable expression systems. Finally, the incidence of DeltaTau-induced cell death was augmented by expression of Abeta precursor protein (APP) or Swedish APP mutant. Taken together, these results suggest that the caspase-3 cleavage product of Tau may contribute to the progression of neuronal cell death in Alzheimer's disease.
MeSH terms
Amyloid beta-Protein Precursor/pharmacologyApoptosis/drug effects*Blotting, WesternCaspase 3Caspases/antagonists & inhibitorsCaspases/metabolism*Cell LineCells, CulturedEnzyme Inhibitors/pharmacologyHumansIndicators and ReagentsPeptide Fragments/geneticsPeptide Fragments/toxicityPlasmids/geneticsRecombinant Proteins/pharmacologyTransfectionbeta-Galactosidase/biosynthesistau Proteins/geneticstau Proteins/metabolism*tau Proteins/toxicity*
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주묵, 인희
Full Text Link
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.