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

Neurochemical Research

Volumn 32, Issue 6, 2007, Pages 1016-1023

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

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^b Korea University   (South Korea)

Author keywords

Secretase; A ; Alzheimer; APP; PEN 2

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; ANTERIOR PHARYNX DEFECTIVE 1 PROTEIN; GAMMA SECRETASE; NICASTRIN; PRESENILIN 2;

ALZHEIMER DISEASE; ARTICLE; CELL CULTURE; CELL LINE; CONTROLLED STUDY; DNA TRANSFECTION; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE AMPLIFICATION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; HYBRID GENE; NUCLEOTIDE SEQUENCE; PLASMID; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PROCESSING;

AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; BLOTTING, WESTERN; CELL LINE, TUMOR; DNA; DNA PRIMERS; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PRESENILIN-2; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; TRANSFECTION;

EID: 34248158120     PISSN: 03643190     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11064-006-9262-0     Document Type: Article

References (17)

1. Kimberly WT, LaVoie MJ, Ostazewski BL et al (2003) Gamma-secretase is amembrane protein complex comprised of presenilin, nicastrin, Aph-1, and PEN-2. Proc Natl Acad Sci USA 100:6382-6387
2. Francis R, McGrath G, Zhang J et al (2002) aph-1 and PEN-2 are required for Notch pathway signaling, gama-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3:85-97
3. Crystal AS, Morais VA, Pierson TC et al (2003) Presenilin modulates PEN-2 levels posttranslationally by protecting it form proteasomal degradation. J Biol Chem 278: 20117-20123
4. Bergman A, Hansson EM, Pursglove SE et al (2004) Pen-2 is sequestered the endoplasmic reticulum and subjected to ubiquitylation and proteasome-mediated degradation in the absence of presenilin. J Biol Chem 279:16744-16753
5. Takasugi N, Tomita T, Hayaashi I et al (2003) The role of presenilin cofactors in the γ-secretase complex. Nature 422:438-441
6. Kim SH, Ikeuchi T, Yu C et al (2003) Regulated hyperaccumulation of presenilin-1 and the "gamma-secretase" complex. Evidence for differential intramembranous processing of transmembrane substrates. J Biol Chem 278:33992-34002
7. Hasegawa H, Sanjo N, Chen F et al (2004) Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes. J Biol Chem 279:46455-46463
8. Steiner H, Winkler E, Edbauer D et al (2002) PEN-2 is an integral component of thegamma-secretase complex required for coordinated expression of presenilin and nicastrin. J Biol Chem 277:39062-39065
9. Prokop S, Shirotani K, Edbauer D et al (2004) Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the γ-secretase complex. J Biol Chem 279:23255-23261
10. Luo WJ, Wang H, Li H et al (2003) PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem 278:7850-7854
11. Murphy MP, Das P, Nyborg AC et al (2003) Overexpression of nicastrin increase Abeta production. FASEB J 17:1138-1140
12. Hu Y, Ye Y, Fortini ME (2002) Nicastrin is required for γ-secretase cleavage of the Drosophila Notch receptor. Dev Cell 2:69-78
13. Min SH, Cho JS, Oh JH et al (2005) Tau and GSK3 dephosphorylations are required for regulating Pin1 phosphorylation. Neurochem Res 30:955-961
14. Hwang DY, Chae KR, Kang TS et al (2002) Alterations in behavior, amyloid β-42, caspase-3, and cox-2 in mutant PS2 transgenic mouse model of Alzheimer's disease. FASEB J 16:805-813
15. Hwang DY, Cho JS, Lee SH et al (2005) Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-contolled APPsw. Exp Neurol 186:20-32
16. Marlow L, Cain M, Pappolla MA et al (2003) Beta-secretase processing of the Alzheimer's amyloid protein precursor (APP). J Mol Neuro 20:233-239
17. Prokop S, Shirotani K, Edbauer D et al (2004) Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex. J Biol Chem 279:23255-23261