Crossref journal-article
Annual Reviews
Annual Review of Neuroscience (22)
Abstract

▪ Abstract  Intensive studies of three proteins—Presenilin, Notch, and the amyloid precursor protein (APP)—have led to the recognition of a direct intersection between early development and late-life neurodegeneration. Notch signaling mediates many different intercellular communication events that are essential for determining the fates of neural and nonneural cells during development and in the adult. The Notch receptor acts in a core pathway as a membrane-bound transcription factor that is released to the nucleus by a two-step cleavage mechanism called regulated intramembrane proteolysis (RIP). The second cleavage is effected by Presenilin, an unusual polytopic aspartyl protease that apparently cleaves Notch and numerous other single-transmembrane substrates within the lipid bilayer. Another Presenilin substrate, APP, releases the amyloid ß-protein that can accumulate over time in limbic and association cortices and help initiate Alzheimer's disease. Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease.

Bibliography

Selkoe, D., & Kopan, R. (2003). NOTCH ANDPRESENILIN: Regulated Intramembrane Proteolysis Links Development and Degeneration. Annual Review of Neuroscience, 26(1), 565–597.

Authors 2
  1. Dennis Selkoe (first)
  2. Raphael Kopan (additional)
References 248 Referenced 521
  1. 10.1186/1471-213X-1-13
  2. 10.1016/S0959-437X(02)00336-2
  3. 10.1016/0168-9525(91)90220-K
  4. 10.1002/(SICI)1521-1878(200003)22:3<264::AID-BIES8>3.3.CO;2-D
  5. 10.1101/gad.987402
  6. 10.1016/S0092-8674(00)00198-7
  7. 10.1002/(SICI)1097-4547(19981015)54:2<125::AID-JNR1>3.3.CO;2-C
  8. 10.1016/S1534-5807(02)00215-0
  9. 10.1016/S0169-328X(99)00119-9
  10. 10.1046/j.1471-4159.2000.0750583.x
  11. 10.1074/jbc.M008268200
  12. 10.1016/S0306-4522(99)00157-8
  13. 10.1016/S0960-9822(00)00633-3
  14. 10.1016/S0092-8674(00)80336-0
  15. 10.1016/S0896-6273(00)80230-5
  16. 10.1016/S0092-8674(00)81180-0
  17. 10.1016/S0960-9822(99)80313-3
  18. 10.1093/genetics/147.1.177 / Genetics by Brennan K (1997)
  19. 10.1006/dbio.1999.9501
  20. 10.1016/S1097-2765(00)80417-7
  21. 10.1016/S0092-8674(00)80675-3
  22. 10.1038/35019075
  23. 10.1006/dbio.2000.9992
  24. 10.1038/2673
  25. 10.1007/BF02740668
  26. 10.1016/S0896-6273(00)80274-3
  27. 10.1074/jbc.273.6.3205
  28. 10.1242/dev.128.5.689 / Development by Chambers CB (2001)
  29. 10.1016/S0959-4388(99)00017-3
  30. 10.1074/jbc.M205093200
  31. 10.1016/S0959-437X(02)00326-X
  32. 10.1038/375761a0
  33. 10.1038/ncb1201-1129
  34. 10.1038/nm0197-67
  35. 10.1242/dev.121.5.1533 / Development by Conlon RA (1995)
  36. 10.1093/genetics/152.2.567 / Genetics by Cornell M (1999)
  37. 10.1242/dev.120.10.2901 / Development by Crittenden SL (1994)
  38. 10.1046/j.1471-4159.2001.00516.x
  39. 10.1016/S1534-5807(01)00091-0
  40. 10.1242/dev.124.6.1139 / Development by de la Pompa JL (1997)
  41. 10.1038/19083
  42. 10.1038/34910
  43. 10.1101/gad.13.21.2801
  44. 10.1038/383710a0
  45. 10.1074/jbc.M111571200
  46. 10.1073/pnas.97.22.11692
  47. 10.1016/S0092-8674(00)80561-9
  48. 10.1038/35017062
  49. 10.1073/pnas.052436599
  50. 10.1021/bi00043a024
  51. 10.1016/S0959-4388(02)00287-8
  52. 10.1006/nbdi.2001.0447
  53. 10.4049/jimmunol.169.4.1817
  54. 10.1016/S1534-5807(02)00189-2
  55. 10.1016/S0960-9822(00)80114-1
  56. 10.1101/gad.991602
  57. 10.1146/annurev.neuro.25.030702.130823
  58. 10.1016/S0896-6273(00)81172-1
  59. 10.1016/S1097-2765(00)80219-1
  60. 10.1242/dev.126.16.3573 / Development by Gho M (1999)
  61. 10.1016/S0896-6273(00)81007-7
  62. 10.1242/dev.117.2.431 / Development by Giniger E (1993)
  63. 10.1242/dev.127.11.2481 / Development by Goutte C (2000)
  64. 10.1073/pnas.022523499
  65. 10.1006/mcne.1997.0610
  66. 10.1074/jbc.C100357200
  67. 10.1074/jbc.M101343200
  68. 10.1126/science.286.5441.916
  69. 10.1242/dev.125.23.4637 / Development by Haddon C (1998)
  70. 10.1242/dev.125.3.359 / Development by Haddon C (1998)
  71. 10.1242/dev.126.15.3415 / Development by Hamada Y (1999)
  72. 10.1242/dev.127.12.2593 / Development by Handler M (2000)
  73. 10.1093/hmg/11.21.2615
  74. 10.1016/0092-8674(91)90263-X
  75. 10.1242/dev.117.3.1113 / Development by Heitzler P (1993)
  76. 10.1073/pnas.96.21.11872
  77. 10.1038/35017105
  78. 10.1038/35019553
  79. 10.1002/jnr.10263
  80. 10.1101/gad.975202
  81. 10.1016/S1534-5807(01)00105-8
  82. 10.1016/S0959-437X(00)00231-8
  83. 10.1093/genetics/145.2.359 / Genetics by Hukriede NA (1997)
  84. 10.1242/dev.124.17.3427 / Development by Hukriede NA (1997)
  85. 10.1038/35016111
  86. 10.1128/MCB.21.12.3888-3900.2001
  87. 10.1016/S0959-437X(99)80066-5
  88. 10.1016/0896-6273(94)90458-8
  89. 10.1242/dev.125.22.4531 / Development by Jacobsen TL (1998)
  90. 10.1021/bi00069a001
  91. 10.1016/S0959-4388(00)00136-7
  92. 10.1083/jcb.200201123
  93. 10.1016/S1357-2725(97)89968-2
  94. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS. 2001. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature414:643–48 (10.1038/414643a)
  95. 10.1046/j.1432-0436.2001.680208.x
  96. 10.1016/S0092-8674(02)00970-4
  97. 10.1016/S0925-4773(02)00120-X
  98. 10.1074/jbc.M210179200
  99. 10.1074/jbc.272.17.11006
  100. 10.1073/pnas.1037392100
  101. 10.1074/jbc.M204446200
  102. 10.1074/jbc.275.5.3173
  103. 10.1074/jbc.C100447200
  104. 10.1146/annurev.cellbio.13.1.333
  105. 10.1146/annurev.ne.15.030192.001343
  106. 10.1242/jcs.112.19.3289 / J. Cell Sci. by Klueg KM (1999)
  107. 10.1016/S0955-0674(97)80085-3
  108. 10.1242/jcs.115.6.1095 / J. Cell Sci. by Kopan R (2002)
  109. 10.1016/S0959-4388(96)80090-0
  110. 10.1006/mcne.1999.0783
  111. 10.1016/S1534-5807(01)00095-8
  112. 10.1101/gad.14.11.1343 / Genes Dev. by Krebs LT (2000)
  113. 10.1016/S0378-1119(96)00673-7
  114. 10.1016/S0021-9258(17)32325-6 / J. Biol. Chem. by Ladror US (1994)
  115. 10.1016/S1534-5807(01)00092-2
  116. 10.1074/jbc.M206872200
  117. {'key': 'b117', 'first-page': 'S176', 'volume': '23', 'author': 'LaVoie M', 'year': '2002', 'journal-title': 'Neurobiol. Aging'} / Neurobiol. Aging by LaVoie M (2002)
  118. 10.1074/jbc.M110371200
  119. 10.1074/jbc.C200148200
  120. 10.1038/nm1096-1146
  121. 10.1038/377351a0
  122. 10.1006/dbio.2001.0486
  123. 10.1159/000064948
  124. 10.1126/science.7638622
  125. 10.1016/S0959-4388(96)80002-X
  126. 10.1006/scdb.1998.0266
  127. 10.1073/pnas.95.12.7109
  128. 10.1038/35015085
  129. 10.1073/pnas.032395699
  130. 10.1073/pnas.96.6.3053
  131. 10.1101/gad.942302
  132. 10.1038/35053522
  133. 10.1073/pnas.95.14.8108
  134. 10.1016/S1534-5807(01)00109-5
  135. 10.1016/S0166-2236(00)01888-9
  136. 10.1093/emboj/21.8.1948
  137. 10.1074/jbc.M201979200
  138. 10.1242/dev.124.8.1485 / Development by Micchelli CA (1997)
  139. 10.1074/jbc.M110023200
  140. {'key': 'b140', 'first-page': 'S209', 'volume': '23', 'author': 'Moehlmann T', 'year': '2002', 'journal-title': 'Neurobiol. Aging'} / Neurobiol. Aging by Moehlmann T (2002)
  141. 10.1073/pnas.112686799
  142. 10.1038/35019000
  143. 10.1016/S0960-9822(01)00224-X
  144. 10.1016/S0955-0674(00)00269-6
  145. 10.1006/dbio.2000.9960
  146. 10.1016/S1097-2765(00)80416-5
  147. 10.1016/S0960-9822(00)00578-9
  148. 10.1016/S0896-6273(00)80637-6
  149. 10.1002/jcb.1110
  150. 10.1126/science.1065412
  151. 10.1016/S0896-6273(01)00214-8
  152. 10.1074/jbc.M103992200
  153. 10.1242/dev.121.10.3291 / Development by Oka C (1995)
  154. 10.1038/35075094
  155. Okajima T, Irvine KD. 2002. Regulation of notch signaling by o-linked fucose. Cell111:893–904 (10.1016/S0092-8674(02)01114-5)
  156. 10.1093/emboj/cdf541
  157. 10.1093/emboj/cdf549
  158. 10.1016/S0092-8674(00)80335-9
  159. 10.1006/scdb.1998.0263
  160. 10.1074/jbc.M204445200
  161. 10.1242/dev.127.7.1373 / Development by Parks AL (2000)
  162. 10.1016/S1534-5807(01)00093-4
  163. 10.1007/PL00000685
  164. 10.1126/science.282.5392.1281
  165. 10.1006/nbdi.1997.0129
  166. 10.1093/hmg/11.9.1037
  167. 10.1016/0092-8674(94)90105-8
  168. 10.1097/00001756-200110290-00035
  169. 10.1126/science.283.5398.91
  170. 10.1016/S0896-6273(00)80999-X
  171. 10.1016/S0960-9822(01)00562-0
  172. 10.1074/jbc.272.39.24536
  173. 10.1016/S1097-2765(00)80006-4
  174. 10.1074/jbc.274.51.36801
  175. 10.1073/pnas.96.6.3263
  176. 10.1038/71104
  177. 10.1038/376775a0
  178. 10.1006/dbio.1999.9483
  179. 10.1083/jcb.151.6.1345
  180. 10.1093/embo-reports/kve180
  181. 10.1074/jbc.M909624199
  182. 10.1038/nm0896-864
  183. 10.1002/(SICI)1096-9861(20000306)418:2<121::AID-CNE1>3.3.CO;2-D
  184. 10.1038/30756
  185. 10.1038/30756
  186. 10.1073/pnas.94.10.5090
  187. 10.1146/annurev.cb.10.110194.002105
  188. 10.1126/science.286.5440.741
  189. 10.1006/dbio.1997.8723
  190. 10.1016/S0092-8674(00)80244-5
  191. 10.1038/375754a0
  192. 10.1074/jbc.M103473200
  193. 10.1016/S0959-437X(97)80083-4
  194. 10.1006/scdb.1998.0265
  195. 10.1038/nrn785
  196. 10.1073/pnas.92.14.6592
  197. 10.1083/jcb.152.4.785
  198. 10.1242/dev.124.23.4769 / Development by Sotillos S (1997)
  199. 10.1074/jbc.273.48.32322
  200. 10.1074/jbc.274.40.28669
  201. 10.1038/35041097
  202. 10.1016/S0959-437X(02)00324-6
  203. 10.1016/S1097-2765(00)00061-7
  204. 10.1038/19091
  205. 10.1242/dev.122.8.2465 / Development by Sun X (1996)
  206. 10.1242/dev.124.17.3439 / Development by Sun X (1997)
  207. 10.1016/S0092-8674(01)00224-0
  208. 10.1101/gad.8.6.707
  209. 10.1128/MCB.18.1.644
  210. 10.1016/S0896-6273(00)80291-3
  211. 10.1074/jbc.272.45.28415
  212. 10.1093/emboj/19.20.5460
  213. 10.1016/S0014-5793(02)02802-8
  214. 10.1073/pnas.94.5.2025
  215. 10.1242/dev.126.24.5725 / Development by Tomlinson A (1999)
  216. 10.1016/S0014-5793(01)03278-1
  217. 10.1016/S0959-437X(02)00327-1
  218. 10.1242/jcs.113.23.4313 / J. Cell Sci. by Varnum-Finney B (2000)
  219. 10.1002/dvdy.1145
  220. 10.1016/S0896-6273(00)00028-3
  221. 10.1242/dev.124.22.4435 / Development by Wang S (1997)
  222. 10.1021/bi015794o
  223. 10.1038/nm0397-328
  224. 10.1126/science.1070925
  225. 10.1242/dev.124.23.4759 / Development by Wen C (1997)
  226. 10.1074/jbc.275.13.9099
  227. 10.1242/dev.124.3.693 / Development by Wettstein DA (1997)
  228. 10.1038/35018575
  229. 10.1021/jm970621b
  230. 10.1021/bi991080q
  231. 10.1126/science.1073844
  232. 10.1038/19077
  233. 10.1038/387288a0
  234. 10.1128/MCB.21.21.7403-7415.2001
  235. 10.1016/S0959-4388(99)00020-3
  236. 10.1073/pnas.94.15.8208
  237. Xia X, Wang P, Sun X, Soriano S, Shum W-K, et al. 2002. The aspartate-257 of Presenilin-1 is indispensable for mouse development and production of ß-amyloid peptides through ß-catenin-independent mechanisms. Proc. Natl. Acad. Sci. USA99:8760–65 (10.1073/pnas.132045399)
  238. 10.1074/jbc.274.46.32543
  239. 10.1074/jbc.M110871200
  240. 10.1038/19096
  241. 10.1016/S0960-9822(01)00527-9
  242. 10.1074/jbc.C100410200
  243. 10.1074/jbc.273.26.16470
  244. 10.1038/35024009
  245. 10.1101/gad.12.8.1086
  246. 10.1074/jbc.M105375200
  247. 10.1038/35017108
  248. 10.1128/MCB.21.18.6222-6232.2001
Dates
Type When
Created 22 years, 4 months ago (April 21, 2003, 8:15 p.m.)
Deposited 2 years, 3 months ago (April 26, 2023, 1:06 a.m.)
Indexed 3 weeks, 1 day ago (July 30, 2025, 8:23 p.m.)
Issued 22 years, 5 months ago (March 1, 2003)
Published 22 years, 5 months ago (March 1, 2003)
Published Print 22 years, 5 months ago (March 1, 2003)
Funders 0

None

@article{Selkoe_2003, title={N<scp>OTCH AND</scp>P<scp>RESENILIN</scp>: Regulated Intramembrane Proteolysis Links Development and Degeneration}, volume={26}, ISSN={1545-4126}, url={http://dx.doi.org/10.1146/annurev.neuro.26.041002.131334}, DOI={10.1146/annurev.neuro.26.041002.131334}, number={1}, journal={Annual Review of Neuroscience}, publisher={Annual Reviews}, author={Selkoe, Dennis and Kopan, Raphael}, year={2003}, month=mar, pages={565–597} }