{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:24:26Z","timestamp":1791145466834,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,2,16]]},"abstract":"<jats:p>\n                    Mutations within the Presenilin-2 (PS-2) gene are associated with\n early onset familial Alzheimer\u2019s disease. The gene encodes a polytopic\n transmembrane protein that undergoes endoproteolytic processing\n resulting in the generation of N-terminal and C-terminal fragments\n (CTFs). PS-2 is also cleaved by proteases of the caspase family during\n apoptotic cell death. CTFs of PS-2 were shown to inhibit\n apoptosis, suggesting an important role in the regulation of\n programmed cell death. Recently, we found that the CTF of PS-2 is\n phosphorylated\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We mapped the\n                    <jats:italic>in vivo<\/jats:italic>\n                    phosphorylation sites of PS-2 to serine residues 327 and 330, which are\n localized immediately adjacent to the cleavage sites of caspases after\n aspartate residues 326 and 329. Phosphorylation of PS-2 inhibits its\n cleavage by caspase-3. This effect can be mimicked by substitutions of\n serines 327 and 330 by aspartate or glutamate. In addition, the\n uncleavable form of PS-2 CTF was found to enhance its\n antiapoptotic properties, leading to a slower progression of\n apoptosis. These results demonstrate that PS-2 cleavage as well\n as its function in apoptosis can be regulated by protein\n phosphorylation. Alterations in the phosphorylation of PS-2 may\n therefore promote the pathogenesis of AD by affecting the\n susceptibility of neurons to apoptotic stimuli.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.4.1391","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"1391-1396","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":103,"title":["Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis"],"prefix":"10.1073","volume":"96","author":[{"given":"Jochen","family":"Walter","sequence":"first","affiliation":[{"name":"Central Institute of Mental Health, Department of Molecular\r Biology, J5, 68159 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Schindzielorz","sequence":"additional","affiliation":[{"name":"Central Institute of Mental Health, Department 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