TY - JOUR
T1 - Increased expression of presenilin 2 inhibits protein synthesis
AU - Gamliel, Amir
AU - Teicher, Carmit
AU - Michaelson, Daniel M.
AU - Pradier, Laurent
AU - Hartmann, Tobias
AU - Beyreuther, Konrad
AU - Stein, Reuven
N1 - Funding Information:
We thank Walter Gams for critically reading the manuscript; Y. Harada (Faculty of Agriculture and Life Science, Hirosaki University) for providing cultures; Karin Rosendahl-Peters for preparing agar media; and Willem Nieuwenhuize for assisting in the experimental work. This study has been carried out with financial support from the Commission of the European Communities, Agriculture and Fisheries (FAIR) specific RTD programme, CT 95-0725, ‘Development of diagnostic methods and a rapid field kit for monitoring Monilinia brown rot of stone and pome fruit, especially M. fructicola’. It does not necessarily reflect its views and in no way anticipates the Commission’s future policy in this area.
PY - 2002
Y1 - 2002
N2 - Mutations in the presenilin genes PS1 and PS2 are a major cause of early onset familial Alzheimer's disease (AD). Previous studies have suggested that presenilins have several functions, including γ-secretase activity. It was also shown that presenilin expression is increased in the brains of some AD patients and ischemic rodents. The present study examines the effect of increased presenilin expression on protein synthesis. We show here that overexpression of wild-type PS2 (PS2wt) or PS2 mutant containing the FAD mutation N1411 (PS2mut) in various cell lines inhibits the synthesis of coexpressed reporter and endogenous proteins. Furthermore, endogenous PS2 seems to be needed for translation inhibition since PS2 null fibroblasts were translationally more active than PS2+/+ fibroblasts under conditions known to inhibit translation. Overexpression of PS1 also appeared to cause inhibition of protein synthesis, but its effect was much weaker than that of PS2. Taken together, the results suggest that increased expression of PS2 and possibly also of PS1 inhibits translation and that presenilins may function as regulators of protein synthesis.
AB - Mutations in the presenilin genes PS1 and PS2 are a major cause of early onset familial Alzheimer's disease (AD). Previous studies have suggested that presenilins have several functions, including γ-secretase activity. It was also shown that presenilin expression is increased in the brains of some AD patients and ischemic rodents. The present study examines the effect of increased presenilin expression on protein synthesis. We show here that overexpression of wild-type PS2 (PS2wt) or PS2 mutant containing the FAD mutation N1411 (PS2mut) in various cell lines inhibits the synthesis of coexpressed reporter and endogenous proteins. Furthermore, endogenous PS2 seems to be needed for translation inhibition since PS2 null fibroblasts were translationally more active than PS2+/+ fibroblasts under conditions known to inhibit translation. Overexpression of PS1 also appeared to cause inhibition of protein synthesis, but its effect was much weaker than that of PS2. Taken together, the results suggest that increased expression of PS2 and possibly also of PS1 inhibits translation and that presenilins may function as regulators of protein synthesis.
UR - http://www.scopus.com/inward/record.url?scp=0036152625&partnerID=8YFLogxK
U2 - 10.1006/mcne.2001.1068
DO - 10.1006/mcne.2001.1068
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 11817902
AN - SCOPUS:0036152625
SN - 1044-7431
VL - 19
SP - 111
EP - 124
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 1
ER -