PEN-2 overexpression induces γ-secretase protein and its activity with amyloid β-42 production

Su J. Seo, Dae Y. Hwang, Jung S. Cho, Kab R. Chae, Chuel K. Kim, Sun B. Shim, Seung W. Jee, Su H. Lee, Ji S. Sin, Soo Y. Choi, Joon Kim, Yong K. Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


PEN-2 is a component of the γ-secretase complex, which is involved in the cleavage of the β-amyloid precursor protein. The aim of this study was to determine the mechanism by which PEN-2 overexpression regulates γ-secretase expression and the production of Aβ-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 γ-secretase activity and its proteins, including PS1-CTF, APH-1, and nicastrin, thus production of Aβ-42, (ii) co-transfection of human PEN-2 with both hPS2m and APPsw exerted no more profound effects on the induction of γ-secretase proteins and its activity than did transfection with hPEN-2 alone. Thus, PEN-2 overexpression may facilitate assembly into the more active γ-secretase complex, and may also induce an increase in activity, thus affecting Aβ-42 production.

Original languageEnglish
Pages (from-to)1016-1023
Number of pages8
JournalNeurochemical Research
Issue number6
Publication statusPublished - 2007 Jun

Bibliographical note

Funding Information:
Acknowledgments This research was supported by grants to Dr. Yong K. Kim from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A040042) and the Korea FDA.


  • APP
  • Alzheimer
  • PEN-2
  • γ-Secretase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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