APP gamma-secretase
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Function
- substrates of gamma-secretase include:
- the C99 & C83 peptides of the amyloid precursor protein (APP) appear to be incidental substrates of gamma-secretase[5]
- removal of the ectodomain is required before gamma-secretase can cleave APP[7]
- gamma-Secretase cleaves APP to form the C-terminus of the A4 peptide; there may be many sites of activity[1]; A4 peptides of 39-42 amino acid residues may be formed
Structure
- core complex:
- other components associated with the core complex include
Compartment
- APP gamma-secretase may be active in endoplasmic reticulum, GOLGI, or within endosomes
More general terms
Additional terms
- A4 amyloid peptide; beta-peptide
- alpha catenin
- amyloid precursor protein; A4/beta amyloid precursor protein (APP)
- Aph-1 protein or homolog of C. elegans anterior pharynx defective 1
- APP secretase
- beta catenin
- nicastrin (NCSTN, KIAA0253, UNQ1874/PRO4317)
- pen-2 protein; presenilin enhancer protein 2; gamma-secretase subunit pen-2 (PSENEN)
- presenilin
- protein
References
- ↑ 1.0 1.1 Ashall F, Goate AM. Role of the beta-amyloid precursor protein in Alzheimer's disease. Trends Biochem Sci. 1994 Jan;19(1):42-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8140621
- ↑ Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature. 2000 Jun 8;405(6787):689-94. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10864326
- ↑ Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature. 2000 Sep 7;407(6800):48-54. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10993067
- ↑ Marx J. Science 294:508, 2001
- ↑ 5.0 5.1 Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274343
- ↑ Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, Takahashi Y, Thinakaran G, Iwatsubo T. The role of presenilin cofactors in the gamma-secretase complex. Nature. 2003 Mar 27;422(6930):438-41. Epub 2003 Mar 16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12660785
- ↑ 7.0 7.1 De Strooper B, Annaert W. Where Notch and Wnt signaling meet. The presenilin hub. J Cell Biol. 2001 Feb 19;152(4):F17-20. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11266476
- ↑ Okochi M, Steiner H, Fukumori A, Tanii H, Tomita T, Tanaka T, Iwatsubo T, Kudo T, Takeda M, Haass C. Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1. EMBO J. 2002 Oct 15;21(20):5408-16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12374741
- ↑ Kimberly WT, Wolfe MS. Identity and function of gamma-secretase. J Neurosci Res. 74(3):353-60. 2003 Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14598311
- ↑ Wilson CA, Doms RW, Lee VM. Distinct presenilin-dependent and presenilin-independent gamma- secretases are responsible for total cellular Abeta production. J Neurosci Res. 74(3):361-9. 2003 Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14598312
- ↑ De Strooper B. Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron. 2003 Apr 10;38(1):9-12. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12691659