Pin1 in Alzheimer's disease: Multiple substrates, one regulatory mechanism?

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1772, Issue 4, 2007, Pages 422-429

  Balastik, Martin ^a   Lim, Jormay ^a   Pastorino, Lucia ^a   Lu, Kun Ping ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Alzheimer's disease; APP; Isomerase; Neurodegeneration; Phosphorylation; Pin1; Tau

Indexed keywords

AMYLOID BETA PROTEIN; PEPTIDYLPROLYL ISOMERASE PIN1;

ALZHEIMER DISEASE; CARCINOGENESIS; DOWN REGULATION; GENE FUNCTION; HUMAN; MOLECULAR DYNAMICS; NEUROPATHOLOGY; NONHUMAN; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SENILE PLAQUE;

ALZHEIMER DISEASE; BRAIN; HUMANS; MODELS, NEUROLOGICAL; NEURONS; PEPTIDYLPROLYL ISOMERASE; REFERENCE VALUES; TAUOPATHIES;

MUS;

EID: 33947140574     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2007.01.006     Document Type: Review

References (109)

1. Nigg E.A. Mitotic kinases as regulators of cell division and its checkpoints. Nat. Rev., Mol. Cell Biol. 2 (2001) 21-32
2. Blangy A., Lane H.A., d'Herin P., Harper M., Kress M., and Nigg E.A. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83 (1995) 1159-1169
3. Qiao M., Shapiro P., Fosbrink M., Rus H., Kumar R., and Passaniti A. Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by cdc2 regulates endothelial cell proliferation. J. Biol. Chem. 281 (2006) 7118-7128
4. Lowe M., Rabouille C., Nakamura N., Watson R., Jackman M., Jamsa E., Rahman D., Pappin D.J., and Warren G. Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis. Cell 94 (1998) 783-793
5. Lu K.P., Hanes S.D., and Hunter T. A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380 (1996) 544-547
6. Lu K.P., Liou Y.C., and Zhou X.Z. Pinning down proline-directed phosphorylation signaling. Trends Cell Biol. 12 (2002) 164-172
7. Ranganathan R., Lu K.P., Hunter T., and Noel J.P. Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent. Cell 89 (1997) 875-886
8. Yaffe M.B., Schutkowski M., Shen M., Zhou X.Z., Stukenberg P.T., Rahfeld J.U., Xu J., Kuang J., Kirschner M.W., Fischer G., Cantley L.C., and Lu K.P. Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science 278 (1997) 1957-1960
9. Lu P.J., Zhou X.Z., Shen M., and Lu K.P. Function of WW domains as phosphoserine- or phosphothreonine-binding modules. Science 283 (1999) 1325-1328
10. Zhou X.Z., Kops O., Werner A., Lu P.J., Shen M., Stoller G., Kullertz G., Stark M., Fischer G., and Lu K.P. Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Mol. Cell 6 (2000) 873-883
11. Weiwad M., Kullertz G., Schutkowski M., and Fischer G. Evidence that the substrate backbone conformation is critical to phosphorylation by p42 MAP kinase. FEBS Lett. 478 (2000) 39-42
12. Brown N.R., Noble M.E., Endicott J.A., and Johnson L.N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. Nat. Cell Biol. 1 (1999) 438-443
13. Schutkowski M., Bernhardt A., Zhou X.Z., Shen M., Reimer U., Rahfeld J.U., Lu K.P., and Fischer G. Role of phosphorylation in determining the backbone dynamics of the serine/threonine-proline motif and Pin1 substrate recognition. Biochemistry 37 (1998) 5566-5575
14. Uchida T., Fujimori F., Tradler T., Fischer G., and Rahfeld J.U. Identification and characterization of a 14 kDa human protein as a novel parvulin-like peptidyl prolyl cis/trans isomerase. FEBS Lett. 446 (1999) 278-282
15. Ayala G., Wang D., Wulf G., Frolov A., Li R., Sowadski J., Wheeler T.M., Lu K.P., and Bao L. The prolyl isomerase Pin1 is a novel prognostic marker in human prostate cancer. Cancer Res. 63 (2003) 6244-6251
16. Shen M., Stukenberg P.T., Kirschner M.W., and Lu K.P. The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins. Genes Dev. 12 (1998) 706-720
17. Crenshaw D.G., Yang J., Means A.R., and Kornbluth S. The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1. EMBO J. 17 (1998) 1315-1327
18. Fujimori F., Takahashi K., Uchida C., and Uchida T. Mice lacking Pin1 develop normally, but are defective in entering cell cycle from G(0) arrest. Biochem. Biophys. Res. Commun. 265 (1999) 658-663
19. Winkler K.E., Swenson K.I., Kornbluth S., and Means A.R. Requirement of the prolyl isomerase Pin1 for the replication checkpoint. Science 287 (2000) 1644-1647
20. Ryo A., Nakamura N., Wulf G., Liou Y.C., and Lu K.P. Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC. Nat. Cell Biol. 3 (2001) 793-801
21. Liou Y.C., Ryo R., Huang H.K., Lu P.J., Bronson R., Fujimori F., Uchidafl U., Hunter T., and Lu K.P. Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 1335-1340
22. Stukenberg P.T., and Kirschner M.W. Pin1 acts catalytically to promote a conformational change in Cdc25. Mol. Cell 7 (2001) 1071-1083
23. Hsu T., McRackan D., Vincent T.S., and Gert De Couet H. Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. Nat. Cell Biol. 3 (2001) 538-543
24. Wulf G.M., Liou Y.C., Ryo A., Lee S.W., and Lu K.P. Role of Pin1 in the regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage. J. Biol. Chem. 277 (2002) 47976-47979
25. Zheng H., You H., Zhou X.Z., Murray S.A., Uchida T., Wulf G., Gu L., Tang X., Lu K.P., and Xiao Z.X.J. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 419 (2002) 849-853
26. Zacchi P., Gostissa M., Uchida T., Salvagno C., Avolio A., Voliniak S., Ronai Z., Blandino G., Schneider C., and Del Sal G. The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 419 (2002) 853-857
27. Ryo A., Suizu F., Yoshida Y., Perrem K., Liou Y.C., Wulf G., Rottapel R., Yamaoka S., and Lu K.P. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol. Cell 12 (2003) 1413-1426
28. Atchison F.W., Capel B., and Means A.R. Pin1 regulates the timing of mammalian primordial germ cell proliferation. Development 130 (2003) 3579-3586
29. Atchison F.W., Means A.R., and Capel B. Spermatogonial depletion in adult Pin1-deficient mice: Pin1 regulates the timing of mammalian primordial germ cell proliferation. Biol. Reprod. 20 (2003) 1989-1997
30. Xu Y.X., Hirose Y., Zhou X.Z., Lu K.P., and Manley J.L. Pin1 modulates the structure and function of human RNA polymerase II. Genes Dev. 17 (2003) 2765-2776
31. Lu K.P. Pinning down cell signaling, cancer and Alzheimer's disease. Trends Biochem. Sci. 29 (2004) 200-209
32. Wulf G.M., Ryo A., Wulf G.G., Lee S.W., Niu T., Petkova V., and Lu K.P. Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J. 20 (2001) 3459-3472
33. Wulf G.M., Ryo A., Wulf G.G., Lee S.W., Niu T., and Lu K.P. Pin1 is overexpressed in breast cancer and potentiates the transcriptional activity of phosphorylated c-Jun towards the cyclin D1 gene. EMBO J. 20 (2001) 3459-3472
34. Ayala G., Wang D., Wulf G., Frolov A., Le R., Wheeler T., Sowadski J.M., Lu K.P., and Bao L. Pin1 is a novel prognostic marker in prostate cancer. Cancer Res. 63 (2003) 6244-6251
35. Bao L., Sauter G., Sowadski J., Lu K.P., and Wang D. Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am. J. Pathol. 164 (2004) 1727-1737
36. Ryo A., Liou Y.C., Wulf G., Nakamura N., Lee S.W., and Lu K.P. Pin1 is an E2F target gene essential for the Neu/Ras-induced transformation of mammary epithelial cells. Mol. Cell. Biol. 22 (2002) 5281-5295
37. Dougherty M.K., Müller J., Ritt D.A., Zhou X.Z., Zhou M., Copeland T.D., Conrads T.P., Veenstra T., Lu K.P., and Morrison D.K. Regulation of Raf-1 by direct feedback phosphorylation. Mol. Cell 17 (2005) 215-224
38. Suizu F., Ryo A., Wulf G., Lim J., and Lu K.P. Pin1 regulates centrosome duplication and its overexpression induces centrosome amplification, chromosome instability and oncogenesis. Mol. Cell. Biol. 26 (2006) 1463-1479
39. Wulf G., Garg P., Liou Y.C., Iglehart D., and Lu K.P. Modeling breast cancer in vivo and ex vivo reveals an essential role of Pin1 in tumorigenesis. EMBO J. 23 (2004) 3397-3407
40. Ryo A., Uemura H., Ishiguro H., Saitoh T., Yamaguchi A., Perrem P., Kubota Y., Lu K.P., and Aoki I. Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer. Clin. Cancer Res. 11 (2005) 7523-7531
41. Lu K.P. Prolyl isomerase Pin1 as a molecular target for cancer diagnostics and therapeutics. Cancer Cells 4 (2003) 175-180
42. Lu K.P., Suizu F., Zhou X.Z., Finn G., Lam P., and Wulf G. Targeting carcinogenesis: a role for the prolyl isomerase Pin1?. Mol. Carcinog. 45 (2006) 397-402
43. Davis F.M., Tsao T.Y., Fowler S.K., and Rao P.N. Monoclonal antibodies to mitotic cells. Proc. Natl. Acad. Sci. U. S. A. 80 (1983) 2926-2930
44. Vincent I., Rosado M., and Davies P. Mitotic mechanisms in Alzheimer's disease?. J. Cell Biol. 132 (1996) 413-425
45. Vincent I., Jicha G., Rosado M., and Dickson D.W. Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J. Neurosci. 17 (1997) 3588-3598
46. Lu K.P., Liou Y.C., and Vincent I. Proline-directed phosphorylation and isomerization in mitotic regulation and in Alzheimer's disease. BioEssays 25 (2003) 174-181
47. Thorpe J.R., Mosaheb S., Hashemzadeh-Bonehi L., Cairns N.J., Kay J.E., Morley S.J., and Rulten S.L. Shortfalls in the peptidyl-prolyl cis-trans isomerase protein Pin1 in neurons are associated with frontotemporal dementias. Neurobiol. Dis. 17 (2004) 237-249
48. Lu P.J., Wulf G., Zhou X.Z., Davies P., and Lu K.P. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 399 (1999) 784-788
49. Thorpe J.R., Morley S.J., and Rulten S.L. Utilizing the peptidyl-prolyl cis-trans isomerase pin1 as a probe of its phosphorylated target proteins. Examples of binding to nuclear proteins in a human kidney cell line and to tau in Alzheimer's diseased brain. J. Histochem. Cytochem. 49 (2001) 97-108
50. Ramakrishnan P., Dickson D.W., and Davies P. Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies. Neurobiol. Dis. 14 (2003) 251-264
51. Liou Y.C., Sun A., Ryo A., Zhou X.Z., Yu Z.X., Huang H.K., Uchida T., Bronson R., Bing G., Li X., Hunter T., and Lu K.P. Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424 (2003) 556-561
52. Pastorino L., Sun A., Lu P.J., Zhou X.Z., Balastik M., Finn G., Wulf G., Lim J., Li S.H., Li X., Xia W., Nicholson L., and Lu K.P. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440 (2006) 528-534
53. Lee V.M., Goedert M., and Trojanowski J.Q. Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24 (2001) 1121-1159
54. Rizzu P., Van Swieten J.C., Joosse M., Hasegawa M., Stevens M., Tibben A., Niermeijer M.F., Hillebrand M., Ravid R., Oostra B.A., Goedert M., van Duijn C.M., and Heutink P. High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am. J. Hum. Genet. 64 (1999) 414-421
55. Hutton M., Lendon C.L., Rizzu P., Baker M., Froelich S., Houlden H., Pickering-Brown S., Chakraverty S., Isaacs A., Grover A., Hackett J., Adamson J., Lincoln S., Dickson D., Davies P., Petersen R.C., Stevens M., de Graaff E., Wauters E., van Baren J., Hillebrand M., Joosse M., Kwon J.M., Nowotny P., Che L.K., Norton J., Morris J.C., Reed L.A., Trojanowski J., Basun H., Lannfelt L., Neystat M., Fahn S., Dark F., Tannenberg T., Dodd P.R., Hayward N., Kwok J.B., Schofield P.R., Andreadis A., Snowden J., Craufurd D., Neary D., Owen F., Oostra B.A., Hardy J., Goate A., van Swieten J., Mann D., Lynch T., and Heutink P. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393 (1998) 702-705
56. Hong M., Zhukareva V., Vogelsberg-Ragaglia V., Wszolek Z., Reed L., Miller B.I., Geschwind D.H., Bird T.D., McKeel D., Goate A., Morris J.C., Wilhelmsen K.C., Schellenberg G.D., Trojanowski J.Q., and Lee V.M. Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science 282 (1998) 1914-1917
57. Spittaels K., Van den Haute C., Van Dorpe J., Bruynseels K., Vandezande K., Laenen I., Geerts H., Mercken M., Sciot R., Van Lommel A., Loos R., and Van Leuven F. Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. Am. J. Pathol. 155 (1999) 2153-2165
58. Lewis J., McGowan E., Rockwood J., Melrose H., Nacharaju P., Van Slegtenhorst M., Gwinn-Hardy K., Paul Murphy M., Baker M., Yu X., Duff K., Hardy J., Corral A., Lin W.L., Yen S.H., Dickson D.W., Davies P., and Hutton M. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25 (2000) 402-405
59. Ishihara T., Hong M., Zhang B., Nakagawa Y., Lee M.K., Trojanowski J.Q., and Lee V.M. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24 (1999) 751-762
60. Brion J.P., Tremp G., and Octave J.N. Transgenic expression of the shortest human tau affects its compartmentalization and its phosphorylation as in the pretangle stage of Alzheimer's disease. Am. J. Pathol. 154 (1999) 255-270
61. Gotz J., Chen F., Barmettler R., and Nitsch R.M. Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem. 276 (2001) 529-534
62. Gotz J., Probst A., Spillantini M.G., Schafer T., Jakes R., Burki K., and Goedert M. Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform. EMBO J. 14 (1995) 1304-1313
63. Tanemura K., Murayama M., Akagi T., Hashikawa T., Tominaga T., Ichikawa M., Yamaguchi H., and Takashima A. Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau. J. Neurosci. 22 (2002) 133-141
64. Cruz J.C., Tseng H.C., Goldman J.A., Shih H., and Tsai L.H. Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40 (2003) 471-483
65. Khurana V., Lu Y., Steinhilb M.L., Oldham S., Shulman J.M., and Feany M.B. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 16 (2006) 230-241
66. Raina A.K., Zhu X., Rottkamp C.A., Monteiro M., Takeda A., and Smith M.A. Cyclin' toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease. J. Neurosci. Res. 61 (2000) 128-133
67. Reynolds C.H., Betts J.C., Blackstock W.P., Nebreda A.R., and Anderton B.H. Phosphorylation sites on tau identified by nanoelectrospray mass spectrometry: differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun N-terminal kinase and P38, and glycogen synthase kinase-3beta. J. Neurochem. 74 (2000) 1587-1595
68. Lim J., and Lu K.P. Pinning down phosphorylated tau and tauopathies. Biochim. Biophys. Acta 1739 (2005) 311-322
69. Hampel H., Buerger K., Kohnken R., Teipel S.J., Zinkowski R., Moeller H.J., Rapoport S.I., and Davies P. Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231. Ann. Neurol. 49 (2001) 545-546
70. Kohnken R., Buerger K., Zinkowski R., Miller C., Kerkman D., DeBernardis J., Shen J., Moller H.J., Davies P., and Hampel H. Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients. Neurosci. Lett. 287 (2000) 187-190
71. Lu P.J., Wulf G., Zhou X.Z., Davies P., and Lu K.P. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 399 (1999) 784-788
72. Hamdane M., Dourlen P., Bretteville A., Sambo A.V., Ferreira S., Ando K., Kerdraon O., Begard S., Geay L., Lippens G., Sergeant N., Delacourte A., Maurage C.A., Galas M.C., and Buee L. Pin1 allows for differential Tau dephosphorylation in neuronal cells. Mol. Cell. Neurosci. 32 (2006) 155-160
73. Allen B., Ingram E., Takao M., Smith M.J., Jakes R., Virdee K., Yoshida H., Holzer M., Craxton M., Emson P.C., Atzori C., Migheli A., Crowther R.A., Ghetti B., Spillantini M.G., and Goedert M. Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J. Neurosci. 22 (2002) 9340-9351
74. Games D., Adams D., Alessandrini R., Barbour R., Berthelette P., Blackwell C., Carr T., Clemens J., Donaldson T., Gillespie F., et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373 (1995) 523-527
75. Gotz J., Chen F., van Dorpe J., and Nitsch R.M. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293 (2001) 1491-1495
76. Hsiao K., Chapman P., Nilsen S., Eckman C., Harigaya Y., Younkin S., Yang F., and Cole G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274 (1996) 99-102
77. Lewis J., Dickson D.W., Lin W.L., Chisholm L., Corral A., Jones G., Yen S.H., Sahara N., Skipper L., Yager D., Eckman C., Hardy J., Hutton M., and McGowan E. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293 (2001) 1487-1491
78. Oddo S., Caccamo A., Shepherd J.D., Murphy M.P., Golde T.E., Kayed R., Metherate R., Mattson M.P., Akbari Y., and LaFerla F.M. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39 (2003) 409-421
79. Nunan J., and Small D.H. Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease. Essays Biochem. 38 (2002) 37-49
80. da Cruz e Silva E.F., and da Cruz e Silva O.A. Protein phosphorylation and APP metabolism. Neurochem. Res. 28 (2003) 1553-1561
81. Pastorino L., and Lu K.P. Phosphorylation of the amyloid precursor protein (APP): is this a mechanism in favor or against Alzheimer's disease?. Neurosci. Res. Commun. 35 (2004) 213-231
82. Gandy S., Czernik A.J., and Greengard P. Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca2+/calmodulin-dependent protein kinase II. Proc. Natl. Acad. Sci. U. S. A. 85 (1988) 6218-6221
83. Suzuki T., Oishi M., Marshak D.R., Czernik A.J., Nairn A.C., and Greengard P. Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein. EMBO J. 13 (1994) 1114-1122
84. Tarr P.E., Contursi C., Roncarati R., Noviello C., Ghersi E., Scheinfeld M.H., Zambrano N., Russo T., and D'Adamio L. Evidence for a role of the nerve growth factor receptor TrkA in tyrosine phosphorylation and processing of beta-APP. Biochem. Biophys. Res. Commun. 295 (2002) 324-329
85. Zambrano N., Bruni P., Minopoli G., Mosca R., Molino D., Russo C., Schettini G., Sudol M., and Russo T. The beta-amyloid precursor protein APP is tyrosine-phosphorylated in cells expressing a constitutively active form of the Abl protoncogene. J. Biol. Chem. 276 (2001) 19787-19792
86. Liu F., Su Y., Li B., Zhou Y., Ryder J., Gonzalez-DeWhitt P., May P.C., and Ni B. Regulation of amyloid precursor protein (APP) phosphorylation and processing by p35/Cdk5 and p25/Cdk5. FEBS Lett. 547 (2003) 193-196
87. Oishi M., Nairn A.C., Czernik A.J., Lim G.S., Isohara T., Gandy S.E., Greengard P., and Suzuki T. The cytoplasmic domain of Alzheimer's amyloid precursor protein is phosphorylated at Thr654, Ser655, and Thr668 in adult rat brain and cultured cells. Mol. Med. 3 (1997) 111-123
88. Iijima K., Ando K., Takeda S., Satoh Y., Seki T., Itohara S., Greengard P., Kirino Y., Nairn A.C., and Suzuki T. Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5. J. Neurochem. 75 (2000) 1085-1091
89. Aplin A.E., Gibb G.M., Jacobsen J.S., Gallo J.M., and Anderton B.H. In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3beta. J. Neurochem. 67 (1996) 699-707
90. Ramelot T.A., and Nicholson L.K. Phosphorylation-induced structural changes in the amyloid precursor protein cytoplasmic tail detected by NMR. J. Mol. Biol. 307 (2001) 871-884
91. Ando K., Iijima K.I., Elliott J.I., Kirino Y., and Suzuki T. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. J. Biol. Chem. 276 (2001) 40353-40361
92. Rippmann J.F., Hobbie S., Daiber C., Guilliard B., Bauer M., Birk J., Nar H., Garin-Chesa P., Rettig W.J., and Schnapp A. Phosphorylation-dependent proline isomerization catalyzed by Pin1 is essential for tumor cell survival and entry into mitosis. Cell Growth Differ. 11 (2000) 409-416
93. Lu P.J., Zhou X.Z., Liou Y.C., Noel J.P., and Lu K.P. Critical role of WW domain phosphorylation in regulating its phosphoserine-binding activity and the Pin1 function. J. Biol. Chem. 277 (2002) 2381-2384
94. Selkoe D.J., Yamazaki T., Citron M., Podlisny M.B., Koo E.H., Teplow D.B., and Haass C. The role of APP processing and trafficking pathways in the formation of amyloid beta-protein. Ann. N. Y. Acad. Sci. 777 (1996) 57-64
95. De Strooper B., and Annaert W. Proteolytic processing and cell biological functions of the amyloid precursor protein. J. Cell Sci. 113 (2000) 1857-1870
96. Esler W.P., and Wolfe M.S. A portrait of Alzheimer secretases-New features and familiar faces. Science 293 (2001) 1449-1454
97. Hardy J., and Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297 (2002) 353-356
98. Mattson M.P. Pathways towards and away from Alzheimer's disease. Nature 430 (2004) 631-639
99. Scheuner D., Eckman C., Jensen M., Song X., Citron M., Suzuki N., Bird T.D., Hardy J., Hutton M., Kukull W., Larson E., Levy-Lahad E., Viitanen M., Peskind E., Poorkaj P., Schellenberg G., Tanzi R., Wasco W., Lannfelt L., Selkoe D., and Younkin S. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat. Med. 2 (1996) 864-870
100. Duff K., Eckman C., Zehr C., Yu X., Prada C.M., Perez-tur J., Hutton M., Buee L., Harigaya Y., Yager D., Morgan D., Gordon M.N., Holcomb L., Refolo L., Zenk B., Hardy J., and Younkin S. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383 (1996) 710-713
101. Borchelt D.R., Thinakaran G., Eckman C.B., Lee M.K., Davenport F., Ratovitsky T., Prada C.M., Kim G., Seekins S., Yager D., Slunt H.H., Wang R., Seeger M., Levey A.I., Gandy S.E., Copeland N.G., Jenkins N.A., Price D.L., Younkin S.G., and Sisodia S.S. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17 (1996) 1005-1013
102. Citron M., Westaway D., Xia W., Carlson G., Diehl T., Levesque G., Johnson-Wood K., Lee M., Seubert P., Davis A., Kholodenko D., Motter R., Sherrington R., Perry B., Yao H., Strome R., Lieberburg I., Rommens J., Kim S., Schenk D., Fraser P., St George Hyslop P., and Selkoe D.J. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 3 (1997) 67-72
103. Takahashi R.H., Milner T.A., Li F., Nam E.E., Edgar M.A., Yamaguchi H., Beal M.F., Xu H., Greengard P., and Gouras G.K. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am. J. Pathol. 161 (2002) 1869-1879
104. Wijsman E.M., Daw E.W., Yu C.E., Payami H., Steinbart E.J., Nochlin D., Conlon E.M., Bird T.D., and Schellenberg G.D. Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2. Am. J. Hum. Genet. 75 (2004) 398-409
105. Segat L., Pontillo A., Annoni G., Trabattoni D., Vergani C., Clerici M., Arosio B., and Crovella S. Pin1 promoter polymorphisms are associated with Alzheimer's disease. Neurobiol. Aging (2005) (Dec 26l; electronic publication ahead of print)
106. Lambert J.C., Bensemain F., Chapuis J., Cottel D., and Amouyel P. Association study of the PIN1 gene with Alzheimer's disease. Neurosci. Lett. 402 (2006) 259-261
107. Sultana R., Boyd-Kimball D., Poon H.F., Cai J., Pierce W.M., Klein J.B., Markesbery W.R., Zhou X.Z., Lu K.P., and Butterfield D.A. Oxidative modification and down-regulation of Pin1 in Alzheimer's disease hippocampus: A redox proteomics analysis. Neurobiol. Aging 27 (2006) 918-925
108. Butterfield D.A., Poon H.F., St Clair D., Keller J.N., Pierce W.M., Klein J.B., and Markesbery W.R. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease. Neurobiol. Dis. 22 (2006) 223-232
109. Roe C.M., Behrens M.I., Xiong C., Miller J.P., and Morris J.C. Alzheimer disease and cancer. Neurology 64 (2005) 895-898