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Dimerization of presenilin-1 in vivo: suggestion of novel regulatory mechanisms leading to higher order complexes.

Abstract：

:A growing body of evidence indicates that presenilins could exist and be active as oligomeric complexes. Using yeast two-hybrid and cell culture analysis, we provide evidence that presenilin-1 (PS1) may self-oligomerize giving rise to specific full-length/full-length homodimers. When expressed in N2A and HEK239T cultured cells, full-length PS1-wt and 5(')myc-PS1-wt form specific homodimers corresponding to twice their molecular weight. The Alzheimer's disease-associated PS1 mutations Y115H, M146L, L392V, deltaE10(PS1(1-289/320-467)), the gamma-secretase dominant negative mutant D257A, and the PS1 polymorphism mutant E318G do not affect their ability to self-oligomerize. Under non-denaturing conditions, endogenous PS1 forms specific homo-oligomers in human cultured cells. The results obtained herein suggest that PS1 associates intramolecularly to form higher order complexes, which may be needed for endoproteolytic cleavage and/or gamma-secretase-associated activity.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hébert SS,Godin C,Tomiyama T,Mori H,Lévesque G

doi

10.1016/s0006-291x(02)02984-4

subject

Has Abstract

pub_date

2003-01-31 00:00:00

pages

119-26

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X02029844

journal_volume

301

pub_type

杂志文章

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