TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity

Nature
Fusheng ChenPaul Fraser

Abstract

The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially ...Continue Reading

References

Jun 15, 1999·The Journal of Cell Biology·C Wen, I Greenwald
Nov 11, 1999·Genes & Development·D B DonovielA Bernstein
May 10, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y M LiS J Gardell
Aug 3, 2001·Nature Cell Biology·F ChenP H St George-Hyslop
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Caroline GoutteJames R Priess
Sep 19, 2002·The Journal of Biological Chemistry·Nicole JenneFelix T Wieland
Mar 28, 2003·Nature·Nobumasa TakasugiTakeshi Iwatsubo
Apr 8, 2003·Nature Cell Biology·Dieter EdbauerChristian Haass
May 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·W Taylor KimberlyDennis J Selkoe
Jun 3, 2004·Nature Reviews. Molecular Cell Biology·Raphael Kopan, Ma Xenia G Ilagan
Oct 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ker-Chau LiTianwei Yu
Oct 4, 2005·The Journal of Clinical Investigation·Jun-Li LuoMichael Karin

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Citations

Nov 27, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Taisuke Tomita
Mar 19, 2013·Protoplasma·Michalina SmolarkiewiczPrzemysław Wojtaszek
Sep 1, 2006·Neurochemical Research·Giuseppe VerdileRalph N Martins
May 21, 2008·Cell Stress & Chaperones·Sun Don Kim, Jinoh Kim
Feb 5, 2010·Nature Structural & Molecular Biology·Yun-wu Zhang, Huaxi Xu
Apr 17, 2009·The Journal of Biological Chemistry·Raphaëlle Pardossi-PiquardPaul E Fraser
Jul 15, 2009·The Journal of Biological Chemistry·Simone EggertEdward H Koo
Aug 28, 2009·The Journal of Biological Chemistry·Raphaëlle Pardossi-PiquardPaul E Fraser
Apr 2, 2011·The Journal of Biological Chemistry·HongBin WangMarcelo G Kazanietz
Feb 9, 2012·The Journal of Biological Chemistry·Ji-Yeun HurLars O Tjernberg
May 6, 2008·The Journal of Biological Chemistry·Kulandaivelu S VetrivelGopal Thinakaran
Nov 26, 2008·The Journal of Biological Chemistry·Haipeng ChengGopal Thinakaran
Nov 28, 2008·The Journal of Biological Chemistry·Lisa PlacanicaYue-Ming Li
Jul 25, 2008·The Journal of Biological Chemistry·Harald SteinerChristian Haass
Feb 19, 2010·Molecular Biology of the Cell·Hongbin Wang, Marcelo G Kazanietz
May 12, 2012·Journal of Experimental Botany·Juan Carlos MontesinosFernando Aniento
Aug 7, 2013·Journal of Experimental Botany·Juan Carlos MontesinosMaría Jesús Marcote
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Ulrike C Müller, Hui Zheng
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Bart De StrooperMichael S Wolfe
Nov 4, 2006·Science·Erik D Roberson, Lennart Mucke
Apr 28, 2010·Molecular and Cellular Biology·Denise StempfleGunter Merdes
Jan 8, 2010·Molecular Cancer Therapeutics·Srinivas KoduruChendil Damodaran
Jul 12, 2007·Neuro-degenerative Diseases·Bianca Van BroeckSamir Kumar-Singh
May 23, 2012·Proteome Science·Stephen Hsueh-Jeng LuPeter St George-Hyslop
Aug 26, 2006·Molecular Neurodegeneration·Hui Zheng, Edward H Koo
Feb 10, 2007·Molecular Neurodegeneration·Kulandaivelu S VetrivelGopal Thinakaran
Mar 8, 2011·Molecular Neurodegeneration·Shengchun LiuWeihong Song
Apr 30, 2011·Molecular Neurodegeneration·Hui Zheng, Edward H Koo
Jan 11, 2011·Molecular Brain·Yun-wu ZhangHuaxi Xu
Jul 23, 2013·Translational Neurodegeneration·Shuting ZhangWeihong Song
Aug 9, 2007·PloS One·Jeroen R P M StratingGerard J M Martens
Nov 26, 2013·Cellular and Molecular Life Sciences : CMLS·Jonghee HanYong-Keun Jung
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rosanna P BakerSinisa Urban

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