title: PEN-2 overexpression induces gamma-secretase protein and its activity with amyloid beta-42 production.
abstract: 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.
authors.affiliation: Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun-dong Eunpyng-ku, Seoul, Korea.
authors.forename: Su J
authors.initials: SJ
authors.lastname: Seo
authors.forename: Dae Y
authors.initials: DY
authors.lastname: Hwang
authors.forename: Jung S
authors.initials: JS
authors.lastname: Cho
authors.forename: Kab R
authors.initials: KR
authors.lastname: Chae
authors.forename: Chuel K
authors.initials: CK
authors.lastname: Kim
authors.forename: Sun B
authors.initials: SB
authors.lastname: Shim
authors.forename: Seung W
authors.initials: SW
authors.lastname: Jee
authors.forename: Su H
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji S
authors.initials: JS
authors.lastname: Sin
authors.forename: Soo Y
authors.initials: SY
authors.lastname: Choi
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Yong K
authors.initials: YK
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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