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Science 26 January 1996:
Vol. 271. no. 5248, pp. 521 - 525
DOI: 10.1126/science.271.5248.521
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Reports

Interfering with Apoptosis: Ca2+-Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3

Pasquale Vito,  Emanuela Lacaná,  Luciano D'Adamio (1)

Two apoptosis-linked genes, named ALG-2 and ALG-3, were identified by means of a functional selection strategy. ALG-2 codes for a Ca2+-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death. ALG-3, a partial complementary DNA that is homologous to the familial Alzheimer's disease gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced apoptosis. These findings suggest that ALG-2 may mediate Ca2+-regulated signals along the death pathway and that cell death may play a role in Alzheimer's disease.


T Cell Molecular Biology Unit, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 111, Bethesda, MD 20892, USA.
(1) To whom correspondence should be addressed.


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Negative Regulation of the Sapk/Jnk Signaling Pathway by Presenilin 1.
J. W. Kim, T.-S. Chang, J. E. Lee, S.-H. Huh, S. W. Yeon, W. S. Yang, C. O. Joe, I. Mook-Jung, R. E. Tanzi, T.-W. Kim, et al. (2001)
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R. Amson, J.-M. Lassalle, H. Halley, S. Prieur, F. Lethrosne, J.-P. Roperch, D. Israeli, M.-C. Gendron, C. Duyckaerts, F. Checler, et al. (2000)
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J. Biol. Chem. 275, 10514-10518
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Regulation of Amyloid Precursor Protein Processing by Presenilin 1 (PS1) and PS2 in PS1 Knockout Cells.
J. J. Palacino, B. E. Berechid, P. Alexander, C. Eckman, S. Younkin, J. S. Nye, and B. Wolozin (2000)
J. Biol. Chem. 275, 215-222
   Abstract »    Full Text »    PDF »
Proteolytic processing and cell biological functions of the amyloid precursor protein.
B De Strooper and W Annaert (2000)
J. Cell Sci. 113, 1857-1870
   Abstract »    PDF »
Presenilin-1 regulates neuronal differentiation during neurogenesis.
M Handler, X Yang, and J Shen (2000)
Development 127, 2593-2606
   Abstract »    PDF »
Activation of Caspase-3 in Single Neurons and Autophagic Granules of Granulovacuolar Degeneration in Alzheimer’s Disease : Evidence for Apoptotic Cell Death.
C. Stadelmann, T. L. Deckwerth, A. Srinivasan, C. Bancher, W. Bruck, K. Jellinger, and H. Lassmann (1999)
Am. J. Pathol. 155, 1459-1466
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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.
A. Herreman, D. Hartmann, W. Annaert, P. Saftig, K. Craessaerts, L. Serneels, L. Umans, V. Schrijvers, F. Checler, H. Vanderstichele, et al. (1999)
PNAS 96, 11872-11877
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Apoptotic Activities of Wild-Type and Alzheimer's Disease-Related Mutant Presenilins in Drosophila melanogaster.
Y. Ye and M. E. Fortini (1999)
J. Cell Biol. 146, 1351-1364
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Interaction of Alzheimer's Presenilin-1 and Presenilin-2 with Bcl-XL. A POTENTIAL ROLE IN MODULATING THE THRESHOLD OF CELL DEATH.
B. J. Passer, L. Pellegrini, P. Vito, J. K. Ganjei, and L. D'Adamio (1999)
J. Biol. Chem. 274, 24007-24013
   Abstract »    Full Text »    PDF »
Membrane Topology of Alzheimer's Disease-related Presenilin 1. EVIDENCE FOR THE EXISTENCE OF A MOLECULAR SPECIES WITH A SEVEN MEMBRANE-SPANNING AND ONE MEMBRANE-EMBEDDED STRUCTURE.
T. Nakai, A. Yamasaki, M. Sakaguchi, K. Kosaka, K. Mihara, Y. Amaya, and S. Miura (1999)
J. Biol. Chem. 274, 23647-23658
   Abstract »    Full Text »    PDF »
Alternative, Non-secretase Processing of Alzheimer's beta -Amyloid Precursor Protein during Apoptosis by Caspase-6 and -8.
L. Pellegrini, B. J. Passer, M. Tabaton, J. K. Ganjei, and L. D'Adamio (1999)
J. Biol. Chem. 274, 21011-21016
   Abstract »    Full Text »    PDF »
Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix.
A. L. Schwarzman, N. Singh, M. Tsiper, L. Gregori, A. Dranovsky, M. P. Vitek, C. G. Glabe, P. H. St. George-Hyslop, and D. Goldgaber (1999)
PNAS 96, 7932-7937
   Abstract »    Full Text »    PDF »
Presenilin Overexpression Arrests Cells in the G1 Phase of the Cell Cycle : Arrest Potentiated by the Alzheimer's Disease PS2(N141I)Mutant.
S. M. Janicki and M. J. Monteiro (1999)
Am. J. Pathol. 155, 135-144
   Abstract »    Full Text »    PDF »
A Myristoylated Calcium-binding Protein that Preferentially Interacts with the Alzheimer's Disease Presenilin 2 Protein.
S. M. Stabler, L. L. Ostrowski, S. M. Janicki, and M. J. Monteiro (1999)
J. Cell Biol. 145, 1277-1292
   Abstract »    Full Text »    PDF »
A Role for Neutral Sphingomyelinase-mediated Ceramide Production in T Cell Receptor-induced Apoptosis and Mitogen-activated Protein Kinase-mediated Signal Transduction.
L. Tonnetti, M.-C. Veri, E. Bonvini, and L. D'Adamio (1999)
J. Exp. Med. 189, 1581-1589
   Abstract »    Full Text »    PDF »
Activation of a Ca2+-permeable cation channel by two different inducers of apoptosis in a human prostatic cancer cell line.
A. A Gutierrez, J. M. Arias, L. Garcia, J. Mas-Oliva, and A. Guerrero-Hernandez (1999)
J. Physiol. 517, 95-107
   Abstract »    Full Text »    PDF »
Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis.
J. Walter, A. Schindzielorz, J. Grunberg, and C. Haass (1999)
PNAS 96, 1391-1396
   Abstract »    Full Text »    PDF »
Cloning of AIP1, a Novel Protein That Associates with the Apoptosis-linked Gene ALG-2 in a Ca2+-dependent Reaction.
P. Vito, L. Pellegrini, C. Guiet, and L. D'Adamio (1999)
J. Biol. Chem. 274, 1533-1540
   Abstract »    Full Text »    PDF »
Contrasting Role of Presenilin-1 and Presenilin-2 in Neuronal Differentiation In Vitro.
C.-S. Hong, L. Caromile, Y. Nomata, H. Mori, D. E. Bredesen, and E. H. Koo (1999)
J. Neurosci. 19, 637-643
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Localisation of presenilin 2 in human and rodent pancreatic islet beta-cells; Met239Val presenilin 2 variant is not associated with diabetes in man.
E. Jaikaran, G Marcon, L Levesque, P. George-Hyslop, P. Fraser, and A Clark (1999)
J. Cell Sci. 112, 2137-2144
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Molecular Cloning of Aralar, a New Member of the Mitochondrial Carrier Superfamily That Binds Calcium and Is Present in Human Muscle and Brain.
A. del Arco and J. Satrustegui (1998)
J. Biol. Chem. 273, 23327-23334
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Molecular Dissection of Domains in Mutant Presenilin 2 That Mediate Overproduction of Amyloidogenic Forms of Amyloid beta  Peptides. INABILITY OF TRUNCATED FORMS OF PS2 WITH FAMILIAL ALZHEIMER'S DISEASE MUTATION TO INCREASE SECRETION OF Abeta 42.
T. Tomita, S. Tokuhiro, T. Hashimoto, K. Aiba, T. C. Saido, K. Maruyama, and T. Iwatsubo (1998)
J. Biol. Chem. 273, 21153-21160
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Regulation of Brain G-protein Go by Alzheimer's Disease Gene Presenilin-1.
A. Smine, X. Xu, K. Nishiyama, T. Katada, P. Gambetti, S. P. Yadav, X. Wu, Y.-C. Shi, S. Yasuhara, V. Homburger, et al. (1998)
J. Biol. Chem. 273, 16281-16288
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A genetic screen for the isolation and characterization of site-specific proteases.
H. J. Sices and T. M. Kristie (1998)
PNAS 95, 2828-2833
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Interaction of Presenilins with the Filamin Family of Actin-Binding Proteins.
W. Zhang, S. W. Han, D. W. McKeel, A. Goate, and J. Y. Wu (1998)
J. Neurosci. 18, 914-922
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Role of Calcium in Glucocorticosteroid-Induced Apoptosis of Thymocytes and Lymphoma Cells: Resurrection of Old Theories by New Findings.
C. W. Distelhorst and G. Dubyak (1998)
Blood 91, 731-734
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To Die or Not to Die: An Overview of Apoptosis and Its Role in Disease.
S. W. Hetts (1998)
JAMA 279, 300-307
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Role of sphingolipid-mediated cell death in neurodegenerative diseases.
T. Ariga, W. D. Jarvis, and R. K. Yu (1998)
J. Lipid Res. 39, 1-16
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Generation of Anti-apoptotic Presenilin-2 Polypeptides by Alternative Transcription, Proteolysis, and Caspase-3 Cleavage.
P. Vito, T. Ghayur, and L. D'Adamio (1997)
J. Biol. Chem. 272, 28315-28320
   Abstract »    Full Text »    PDF »
Increased Apoptosis Arising from Increased Expression of the Alzheimer's Disease-associated Presenilin-2 Mutation (N141I).
S. Janicki and M. J. Monteiro (1997)
J. Cell Biol. 139, 485-495
   Abstract »    Full Text »    PDF »
Appearance of Phosphatidylserine on Apoptotic Cells Requires Calcium-mediated Nonspecific Flip-Flop and Is Enhanced by Loss of the Aminophospholipid Translocase.
D. L. Bratton, V. A. Fadok, D. A. Richter, J. M. Kailey, L. A. Guthrie, and P. M. Henson (1997)
J. Biol. Chem. 272, 26159-26165
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Alzheimer's Presenilin Mutation Sensitizes Neural Cells to Apoptosis Induced by Trophic Factor Withdrawal and Amyloid beta -Peptide: Involvement of Calcium and Oxyradicals.
Q. Guo, B. L. Sopher, K. Furukawa, D. G. Pham, N. Robinson, G. M. Martin, and M. P. Mattson (1997)
J. Neurosci. 17, 4212-4222
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Aberrant Expression of Mitotic Cdc2/Cyclin B1 Kinase in Degenerating Neurons of Alzheimer's Disease Brain.
I. Vincent, G. Jicha, M. Rosado, and D. W. Dickson (1997)
J. Neurosci. 17, 3588-3598
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CD2 Rescues T Cells From T-Cell Receptor/CD3 Apoptosis: A Role for the Fas/Fas-L System.
E. Ayroldi, G. Migliorati, L. Cannarile, R. Moraca, D. V. Delfino, and C. Riccardi (1997)
Blood 89, 3717-3726
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Evidence for a Six-transmembrane Domain Structure of Presenilin 1.
S. Lehmann, R. Chiesa, and D. A. Harris (1997)
J. Biol. Chem. 272, 12047-12051
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Intracellular and secreted Alzheimer beta -amyloid species are generated by distinct mechanisms in cultured hippocampal neurons.
P. J. Tienari, N. Ida, E. Ikonen, M. Simons, A. Weidemann, G. Multhaup, C. L. Masters, C. G. Dotti, and K. Beyreuther (1997)
PNAS 94, 4125-4130
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Bik and Bak Induce Apoptosis Downstream of CrmA but Upstream of Inhibitor of Apoptosis.
K. Orth and V. M. Dixit (1997)
J. Biol. Chem. 272, 8841-8844
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An Apoptosis-inducing Isoform of Neu Differentiation Factor (NDF) Identified Using a Novel Screen for Dominant, Apoptosis-inducing Genes.
S. Grimm and P. Leder (1997)
J. Exp. Med. 185, 1137-1142
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Exploring the Etiology of Alzheimer Disease Using Molecular Genetics.
C. L. Lendon, F. Ashall, and A. M. Goate (1997)
JAMA 277, 825-831
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Life and Death in the Cardiovascular System.
E. T.H. Yeh (1997)
Circulation 95, 782-786
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p53 Expression Induces Apoptosis in Hippocampal Pyramidal Neuron Cultures.
J. Jordan, M. F. Galindo, J. H. M. Prehn, R. R. Weichselbaum, M. Beckett, G. D. Ghadge, R. P. Roos, J. M. Leiden, and R. J. Miller (1997)
J. Neurosci. 17, 1397-1405
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Phosphorylation, Subcellular Localization, and Membrane Orientation of the Alzheimer's Disease-associated Presenilins.
B. De Strooper, M. Beullens, B. Contreras, L. Levesque, K. Craessaerts, B. Cordell, D. Moechars, M. Bollen, P. Fraser, P. St. George-Hyslop, et al. (1997)
J. Biol. Chem. 272, 3590-3598
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Requirement of the Familial Alzheimer's Disease Gene PS2 for Apoptosis. OPPOSING EFFECT OF ALG-3.
P. Vito, B. Wolozin, J. K. Ganjei, K. Iwasaki, E. Lacana, and L. D'Adamio (1996)
J. Biol. Chem. 271, 31025-31028
   Abstract »    Full Text »    PDF »
Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation.
B. Wolozin, K. Iwasaki, P. Vito, J. K. Ganjei, E. Lacanà, T. Sunderland, B. Zhao, J. W. Kusiak, W. Wasco, and L. D'Adamio (1996)
Science 274, 1710-1713
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