Catabolism of endogenous and overexpressed APH1a and PEN2: Evidence for artifactual involvement of the proteasome in the degradation of overexpressed proteins

Biochemical Journal

Volumn 394, Issue 2, 2006, Pages 501-509

  Dunys, Julie ^a   Kawarai, Toshitaka ^b   Wilk, Sherwin ^c   St George Hyslop, Peter ^b   Alves Da Costa, Cristine ^a   Checler, Frédéric ^a  

^a CNRS   (France)

^b UNIVERSITY OF TORONTO   (Canada)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

secretase complex; Anterior pharynx defective 1 homologue (APH1a); Nicastrin; Presenilin enhancer 2 homologue (PEN2); Presenilins; Proteasome

Indexed keywords

CELL CULTURE; ENZYME INHIBITION; ENZYME KINETICS;

CATABOLISM; PRESENILINS; PROTEASOME;

PROTEINS;

ANTERIOR PHARYNX DEFECTIVE 1 PROTEIN; GAMMA SECRETASE; LACTACYSTIN; MYC PROTEIN; NICASTRIN; PRESENILIN 2; PRESENILIN ENHANCER 2; PROTEASOME; PROTEASOME INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL STRAIN HEK293; EMBRYO; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; WESTERN BLOTTING;

ANIMALS; CATTLE; CELL LINE; ENDOPEPTIDASES; FIBROBLASTS; GENE DELETION; GENE EXPRESSION; HUMANS; MEMBRANE PROTEINS; MICE; NEURONS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEINS; RECEPTORS, NOTCH; TRANSFECTION;

ANIMALIA;

EID: 33644781725     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20051197     Document Type: Article

References (50)

1. Checler, F. (1995) Processing of the β-amyloid precursor protein and its regulation in Alzheimer's disease. J. Neurochem. 65, 1431-1444
2. Armogida, M., Petit, A., Vincent, B., Scarzello, S., Alves da Costa, C. and Checler, F. (2001) Endogenous β-amyloid production in presenilin-deficient embryonic mouse fibroblasts. Nat. Cell Biol. 3, 1030-1033
3. Beglopoulos, V., Sun, X., Saura, C. A., Lemere, C. A., Kim, R. D. and Shen, J. (2004) Reduced β-amyloid production and increased inflammatory response in presenilin conditional knockout mice. J. Biol. Chem. 279, 46566-46572
4. Heireman, A., Serneels, L., Annaert, W., Collen, D., Schoonjans, L. and De Strooper, B. (2000) Total inactivation of γ-secretase activity in presenilin-deficient embryonic stem cells. Nat. Cell Biol. 2, 461-462
5. Zhang, Z., Nadeau, P., Song, W., Donoviel, D., Yuan, M., Bernstein, A. and Yankner, B. A. (2000) Presenilins are required for γ-secretase cleavage of βAPP and transmembrane cleavage of Notch. Nat. Cell Biol. 2, 463-465
6. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y-Q., Rogaeva, E., Chen, F., Kawarai, T. et al. (2000) Nicastrin modulates presenilin-mediated notch/glp1 signal transduction and βAPP processing. Nature (London) 407, 48-54
7. Francis, R., McGrath, G., Zhang, J., Ruddy, D. A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M. C. et al. (2002) APH1 and PEN2 are required for notch pathway signaling, γ-secretase cleavage of βAPP, and presenilin protein accumulation. Dev. Cell 3, 85-97
8. Goutte, C., Tsunozaki, M., Hale, V. A. and Priess, J. R. (2002) APH1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. Proc. Natl. Acad. Sci. U.S.A. 99, 775-779
9. Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G. and Iwatsubo, T. (2003) The role of presenilin cofactors in the γ-secretase complex. Nature (London) 422, 438-441
10. Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H. and Haass, C. (2003) Reconstitution of γ-secretase activity. Nat. Cell Biol. 5, 486-488
11. Steiner, H., Winkler, E., Edbauer, D., Prokop, S., Basset, G., Yamasaki, A., Kostka, M. and Haass, C. (2002) PEN2 is an integral component of the γ-secretase complex required for coordinated expression of presenilin and nicastrin. J. Biol. Chem. 277, 39062-39065
12. Luo, W. J., Wang, H., Li, H., Kim, B. S., Shah, S., Lee, H.-J., Thinakaran, G., Kim, T-W., Yu, G. and Xu, H. (2003) PEN2 and APH1 coordinately regulate proteolytic processing of presenilin 1. J. Biol. Chem. 278, 7850-7854
13. Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordstedt, C., Seeger, M. et al. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron. 17, 181-190
14. Prokop, S., Shirotani, K., Edbauer, D., Haass, C. and Steiner, H. (2004) Requirement of PEN2 for stabilization of the presenilin NTF/CTF heterodimer within the γ-secretase complex. J. Biol. Chem. 279, 23255-23261
15. La Voie, M. J., Fraering, P. C., Ostaszewski, B. L., Ye, W., Kimberly, W. T., Wolfe, M. S. and Selkoe, D. J. (2003) Assembly of the γ-secretase complex involves early formation of an intermediate sub-complex of APH1 and nicastrin. J. Biol. Chem. 278, 37213-37222
16. Hu, Y. and Fortini, M. E. (2003) Different cofactor activities in γ-secretase assembly: evidence for a nicastrin-APH1 subcomplex. J. Cell Biol. 161, 685-690
17. Lee, S.-F., Shah, S., Li, H., Yu, C., Han, W. and Yu, G. (2002) Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-β precursor protein and Notch. J. Biol. Chem. 277, 45013-450139
18. Gu, Y., Chen, F., Sanjo, N., Kawarai, T., Hasegawa, H., Duthie, M., Li, W., Ruan, X., Luthra, A., Mount, H. T. J. et al. (2003) APH1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin-nicastrin complexes. J. Biol. Chem. 278, 7374-7380
19. Ma, G., Li, T., Price, D. and Wong, P. C. (2005) APH1a is the principal mammalian APH1 isoform present in γ-secretase complexes during embryonic development. J. Neurosci. 25, 192-198
20. Shirotani, K., Edbauer, D., Prokop, S., Haass, C. and Steiner, H. (2004) Identification of distinct γ-secretase complexes with different APH1 variants. J. Biol. Chem. 279, 41340-41345
21. Hébert, S. S., Serneels, L., Dejaegere, T., Horré, K., Dabrowski, M., Baert, V., Annaert, W., Hartmann, D. and De Strooper, B. (2004) Coordinated and widespread expression of γ-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol. Dis. 17, 260-272
22. Rraering, P. C., La Voie, M. J., Ye, W., Ostaszewski, B. L., Kimberly, W. T., Selkoe, D. J. and Wolfe, M. S. (2004) Detergent-dependent dissociation of active γ-secretase reveals an interaction between PEN2 and PS1-NTR and offers a model for subunit organization within the complex. Biochemistry 43, 323-333
23. Crystal, A. S., Morais, V. A., Rortna, R. R., Carlin, D., Pierson, T. C., Wilson, B., Lee, V. M.-Y. and Doms, R. W. (2004) Presenilin modulates PEN2 levels posttranslationally by protecting it from proteasomal degradation. Biochemistry 43, 3555-3563
24. Bergman, A., Hansson, E., Pursglove, S. E., Farmery, M. R., Lannfelt, L., Lendhal, U., Lundkvist, J. and Näslund, J. (2004) PEN2 is sequestered in the endoplasmic reticulum and subjected to ubiquitylation and proteasome-mediated degradation in the absence of presenilin. J. Biol. Chem. 279, 16744-16753
25. Hasegawa, H., Sanjo, N., Chen, F., Gu, Y.-J., Shier, C., Petit, A., Kawarai, T., Katayama, T., Schmidt, S. D., Mathews, P. M. et al. (2004) Both the sequence and length of the C terminus of PEN2 are critical for intermolecular interactions and function of presenilin complexes. J. Biol. Chem. 279, 46455-46463
26. Alves da Costa, C., Paitel, E., Mattson, M. P., Amson, R., Telerman, A., Ancolio, K. and Checler, F. (2002) Wild-type and mutated presenilin-2 trigger p53-dependent apoptosis and down-regulate presenilin-1 expression in HEK-293 human cells and in murine neurons. Proc. Natl. Acad. Sci. U.S.A. 99, 4043-4048
27. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J. et al. (1999) A presenilin-1 -dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature (London) 398, 518-522
28. Lai, M.-T., Chen, E., Crouthamel, M.-C., DiMuzio-Mower, J., Xu, M., Huang, Q., Price, E., Register, R. B., Shi, X.-P., Donoviel, D. B. et al. (2003) Presenilin-1 and presenilin-2 exhibit distinct yet overlapping γ-secretase activities. J. Biol. Chem. 278, 22475-22481
29. Heber, S., Herms, J., Gajic, V., Hainfellner, J. A., Aguzzi, A., Rülicke, T., Kretzschmar, H., von Koch, C., Sisodia, S. S., Tremml, P. et al. (2000) Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J. Neurosci. 20, 7951-7963
30. Li, T., Ma, G., Cai, H., Price, D. L. and Wong, P. C. (2003) Nicastrin is required for assembly of presenilin/γ-secretase complexes to mediate notch signaling and for processing and trafficking of β-amyloid precursor protein in mammals. J. Neurosci. 23, 3272-3277
31. Vincent, B., Beaudet, A., Dauch, P., Vincent, J. P. and Checler, F. (1996) Distinct properties of neuronal and astrocytic endopeptidase 3.4.24.16: a study on differenciation, subcellular distribution and secretion processes. J. Neurosci. 16, 5049-5059
32. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Bioctiem. 72, 248-259
33. Tanahashi, N., Murakami, Y., Minami, Y., Shimbara, N., Hendil, K. B. and Tanaka, K. (2000) Hybrid proteasomes: Induction by interferon-γ and contribution to ATP-dependent proteolysis. J. Biol. Chem. 275, 14336-14445
34. Wilk, S. and Chen, W.-E. (2001) Purification of the eukaryotic 20 S proteasome. In Current Protocols in Protein Science (Dunn, B., ed.), Unit 21, pp. 6.1-6.9, John Wiley and Sons, New York.
35. Kimberly, W. T., LaVoie, M. J., Ostaszewski, B. L., Ye, W., Wolfe, M. S. and Selkoe, D. J. (2003) γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, APH1 and PEN2. Proc. Natl. Acad. Sci. U.S.A. 100, 6382-6387
36. Fortna, R. R., Crystal, A. S., Morais, V. A., Pijak, D. S., Lee, V. M.-Y. and Doms, R. W. (2004) Membrane topology and nicastrin-enhanced endoproteolysis of APH1, a component of the γ-secretase complex. J. Biol. Chem. 279, 3685-3693
37. Fenteany, G., Standaert, R., Lane, W. S., Choi, S., Corey, E. J. and Schreiber, S. L. (1995) Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science (Washington, D.C.) 268, 726-731
38. Peirera, M. E., Yu, B. and Wilk, S. (1992) Enzymatic changes of the bovine pituitary multicatalytic proteinase complex induced by magnesium ions. Arch. Biochem. Biophys. 294, 1-8
39. Drisaldi, B., Stewart, R. S., Adles, C., Stewart, L. R., Quaglio, E., Biasini, E., Fioriti, L., Chiesa, R. and Harris, D. A. (2003) Mutant PrP is delayed in its exit from the endoplasmic reticulum but neither wild-type nor mutant PrP undergoes retrotranslocation prior to proteasomal degradation. J. Biol. Chem. 278, 21732-21743
40. Biasini, E., Fioriti, L., Ceglia, I., Invernizzi, R., Bertoli, A., Chiesa, R. and Forloni, G. (2004) Proteasome inhibition and aggregation in Parkinson's disease: a comparative study in untransfected and transfected cells. J. Neurocnem. 88, 545-553
41. Fioriti, L., Dossena, S., Stewart, L. R., Stewart, R. S., Harris, D., Forloni, G. and Chiesa, R. (2005) Cytosolic prion protein (PrP) is not toxic in N2a cells and primary neurons expressing pathogenic PrP mutations. J. Biol. Chem. 280, 11320-11328
42. Orlowski, M. and Wilk, S. (2003) Ubiquitin-independent proteolytic functions of the proteasome. Arch. Biochem. Biophys. 415, 1-5
43. Suh, Y.-H. and Checler, F. (2002) Amyloid precursor protein, presenilins and α-synuclein: Molecular pathogenesis and pharmacological applications in Alzheimers' disease. Pharmacol. Rev. 54, 469-525
44. Vassar, R. (2001) The β-secretase, BACE. J. Mol. Neurosci. 17, 157-170
45. Wilson, C. A., Doms, R. W., Zheng, H. and Lee, V. M.-Y. (2002) Presenilins are not required for Aβ42 production in the early secretory pathway. Nat. Neurosci. 5, 849-855
46. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Von Figura, K. and Van Leuven, F. (1998) Deficiency of presenilin 1 inhibits the normal cleavage of amyloid precursor protein. Nature (London) 391, 387-390
47. De Strooper, B. (2003) APH1, PEN2, and nicastrin with presenilin generate an active γ-secretase complex. Neuron 38, 9-12
48. Serneels, L., Dejaegere, T., Craessaerts, K., Horré, K., Jorissen, E., Tousseyn, T., Hébert, S., Coolen, M., Martens, G., Zwijsen, A. et al. (2005) Differential contribution of the three Aph1 genes to γ-secretase activity in vivo. Proc. Natl. Acad. Sci. U.S.A. 102, 1719-1724
49. Ostrowska, H., Wojcik, C., Wilk, S., Omura, S., Kozlowski, L., Stoklosa, T., Worowski, K. and Radziwon, P. (2000) Separation of cathepsin A-like enzyme and the proteasome: evidence that lactacystin/β-lactone is not a specific inhibitor of the proteasome. Int. J. Biochem. Cell Biol. 32, 747-757
50. Herreman, A., Hartmann, D., Annaert, W., Saftig, P., Craessaerts, K., Serneels, L., Umans, L., Schrijvers, V., Checler, F., Vanderstichele, H. et al. (1999) Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc. Natl. Acad. Sci. U.S.A. 96, 11872-11877