{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:40:17Z","timestamp":1777394417099,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T00:00:00Z","timestamp":1485475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2017,2,20]]},"abstract":"<jats:p>\n                    Presenilin-1 (PS1) or presenilin-2 (PS2), nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer-2 (Pen-2) have been considered the minimal essential subunits required to form an active\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -secretase complex. Besides PS, which has been widely believed to function as the catalytic subunit of the complex, the functional roles of the other subunits in the\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -secretase complex remain debatable. In the current study, we set out to determine the role of Pen-2 in\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -secretase activity. To this end, using knockout cells in combination with siRNA and immunoprecipitation approaches, our results revealed that Pen-2 together with presenilin are sufficient to form a functionally active enzyme to process Notch. Specifically, our data demonstrated that Pen-2 plays a crucial role in substrate binding, a mechanism by which Pen-2 contributes directly to the catalytic mechanism of\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -secretase activity. Our data also suggested that there may be different requirements for components to process A\u03b2PP and Notch. This information would be important for therapeutic strategy aimed at inhibition or modulation of\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -secretase activity.\n                  <\/jats:p>","DOI":"10.3233\/jad-161094","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T11:36:37Z","timestamp":1487676997000},"page":"1263-1269","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Pen-2 and Presenilin are Sufficient to Catalyze Notch Processing"],"prefix":"10.1177","volume":"56","author":[{"given":"Chen","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA"},{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Jilin Medical University, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA"},{"name":"School of Life Sciences, Jilin University, Changchun, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA"},{"name":"Department of Cell Biology, Tianjin Medical University, Tianjin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Zhen","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,1,27]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006304"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd938"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.022"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00189-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208164200"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200648200"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01506"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.216978"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12016"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi500489j"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.12.028"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-08-03272.2003"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/34910"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.11872"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/35017105"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400473200"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507993200"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.4.1683"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.16.9390"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209613200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13518"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.373"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.33.20655"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1997.0129"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi972106l"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80291-3"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/35017062"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/35015085"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401789200"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803040200"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3826-09.2010"}],"container-title":["Journal 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