Functional cloning of genes involved in T-cell receptor-induced programmed cell death.
Programmed cell death (PCD) is a normal event under genetic control that regulates the life span of different cell types in multicellular organisms. Among other physiological processes, PCD plays a pivotal role in the regulation of the immune system. Using a functional selection strategy we have isolated and characterized genes involved in T-cell receptor-induced apoptosis. One, ALG-2, is a Ca(2+)-binding protein that participates in regulatory events that occur late in the apoptotic program, where several death signals converge. Another, ALG-3, is a mouse homologue of the chromosome 1 familial Alzheimer's disease gene PS2. ALG-3 codes for a truncated PS2 polypeptide that antagonizes the apoptotic role of PS2. A PS2 mutation associated with Alzheimer's disease generates a molecule with enhanced apoptotic activity indicating that it might accelerate the process of neurodegeneration that occurs in this disease.
D'Adamio
L
L
T-cell Molecular Biology Unit, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Lacanà
E
E
Vito
P
P
D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics*; D003001:Cloning, Molecular / Q000379:methods*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D053766:Presenilin-2; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; C097753:PDCD6 protein, human; C508861:PSEN2 protein, human; C490815:Pdcd6 protein, mouse; D053766:Presenilin-2; C095101:Psen2 protein, mouse; D011948:Receptors, Antigen, T-Cell