PEN-2 overexpression induces gamma-secretase protein and its activity with amyloid beta-42 production.
PEN-2 is a component of the gamma-secretase complex, which is involved in the cleavage of the beta-amyloid precursor protein. The aim of this study was to determine the mechanism by which PEN-2 overexpression regulates gamma-secretase expression and the production of Abeta-42. In order to determine this, a hybrid gene harboring human PEN-2 was constructed, and used in the transfection of SK-N-MC human neuroepitheliomal cells. This cell line was also co-transfected with a combination of human mutant presenilin 2 (hPS2m) and APPsw. Our results indicated that (i) human PEN-2 overexpression induced an increase in gamma-secretase activity and its proteins, including PS1-CTF, APH-1, and nicastrin, thus production of Abeta-42, (ii) co-transfection of human PEN-2 with both hPS2m and APPsw exerted no more profound effects on the induction of gamma-secretase proteins and its activity than did transfection with hPEN-2 alone. Thus, PEN-2 overexpression may facilitate assembly into the more active gamma-secretase complex, and may also induce an increase in activity, thus affecting Abeta-42 production.
Seo
Su J
SJ
Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun-dong Eunpyng-ku, Seoul, Korea.
Hwang
Dae Y
DY
Cho
Jung S
JS
Chae
Kab R
KR
Kim
Chuel K
CK
Shim
Sun B
SB
Jee
Seung W
SW
Lee
Su H
SH
Sin
Ji S
JS
Choi
Soo Y
SY
Kim
Joon
J
Kim
Yong K
YK
D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis*; D053766:Presenilin-2 / Q000096:biosynthesis* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D016229:Amyloid beta-Peptides; D017931:DNA Primers; D010446:Peptide Fragments; D053766:Presenilin-2; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); D004247:DNA; D053829:Amyloid Precursor Protein Secretases