Monoubiquitination and endocytosis direct gamma-secretase cleavage of activated Notch receptor

The Journal of Cell Biology
Neetu Gupta-RossiC Brou

Abstract

Activation of mammalian Notch receptor by its ligands induces TNFalpha-converting enzyme-dependent ectodomain shedding, followed by intramembrane proteolysis due to presenilin (PS)-dependent gamma-secretase activity. Here, we demonstrate that a new modification, a monoubiquitination, as well as clathrin-dependent endocytosis, is required for gamma-secretase processing of a constitutively active Notch derivative, DeltaE, which mimics the TNFalpha-converting enzyme-processing product. PS interacts with this modified form of DeltaE, DeltaEu. We identified the lysine residue targeted by the monoubiquitination event and confirmed its importance for activation of Notch receptor by its ligand, Delta-like 1. We propose a new model where monoubiquitination and endocytosis of Notch are a prerequisite for its PS-dependent cleavage, and discuss its relevance for other gamma-secretase substrates.

References

Sep 28, 1995·Nature·S JarriaultA Israel
Oct 21, 1994·Cell·M E Fortini, S Artavanis-Tsakonas
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·R KopanJ S Nye
Jan 23, 1998·Journal of Medicinal Chemistry·M S WolfeD J Selkoe
Jan 27, 1998·Developmental Biology·L SeugnetM Haenlin
Jun 20, 1998·The Journal of Biological Chemistry·J ZhangE H Koo
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·F LogeatA Israël
Dec 14, 1999·The Journal of Biological Chemistry·W J RayA M Goate
Aug 5, 2000·Molecular and Cellular Neurosciences·J J Lah, A I Levey
Aug 15, 2000·The Journal of Biological Chemistry·L QiuY C Liu
Sep 22, 2000·Trends in Cell Biology·P K JacksonJ D Reimann
Apr 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·K FassbenderT Hartmann
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·E KojroF Fahrenholz
May 10, 2001·Proceedings of the National Academy of Sciences of the United States of America·B Wolozin
Jun 27, 2001·The Journal of Biological Chemistry·N Gupta-RossiA Israël
Sep 19, 2001·The Journal of Biological Chemistry·C BüttnerG Schmalzing
Jan 5, 2002·The Journal of Biological Chemistry·Birgit M JehnWolfgang Bielke
Jan 31, 2002·Current Biology : CB·Eric C Lai
Feb 12, 2002·Nature Cell Biology·Yasuyuki FujitaWalter Birchmeier
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshihito TaniguchiTasuku Honjo
May 29, 2002·The Journal of Biological Chemistry·Dun-Sheng YangPaul E Fraser
Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tobias MoehlmannHarald Steiner
Jul 12, 2002·Journal of Neuroscience Research·Carol HicksGerry Weinmaster
Aug 30, 2002·Current Opinion in Genetics & Development·Sinisa Urban, Matthew Freeman
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·Mark E Fortini

❮ Previous
Next ❯

Citations

Nov 15, 2005·Nature Cell Biology·Ashim MukherjeeSpyros Artavanis-Tsakonas
Sep 9, 2008·Nature Cell Biology·Sander H DiksDanica Zivkovic
Aug 22, 2006·Nature Reviews. Molecular Cell Biology·Sarah J Bray
Aug 22, 2009·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark von Zastrow
Sep 2, 2008·Oncogene·P RizzoL Miele
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sean M BuchananTom Maniatis
Jul 2, 2009·The Journal of Biological Chemistry·Melanie A McGillC Jane McGlade
Sep 3, 2009·The Journal of Biological Chemistry·Yi-Wei HuangLisa A Robinson
May 25, 2010·The Journal of Biological Chemistry·Pavel Montes de OcaFranck Gesbert
Apr 6, 2011·The Journal of Biological Chemistry·Neetu Gupta-RossiAlain Israël
Jun 21, 2011·The Journal of Biological Chemistry·Sheu-Fen LeeGang Yu
Dec 4, 2010·Stem Cells and Development·Christian LangeFederico Calegari
Jul 13, 2007·Molecular Biology of the Cell·Mads LerdrupBo van Deurs
Oct 31, 2007·Molecular and Cellular Biology·Shinji TagamiMasatoshi Takeda
May 18, 2007·Annual Review of Cell and Developmental Biology·Maria Ciofani, Juan Carlos Zúñiga-Pflücker
Mar 23, 2006·Annual Review of Immunology·Adam Mor, Mark R Philips
May 23, 2008·American Journal of Physiology. Cell Physiology·Yuanli LiDaniel Biemesderfer
Jun 10, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Antonio PannutiLucio Miele
Jan 23, 2008·BMC Developmental Biology·Zifei Pei, Nicholas E Baker
Jan 30, 2010·Development·Emily C N Richardson, Franck Pichaud
Jul 17, 2008·PloS One·Patricia ChastagnerChristel Brou
May 1, 2007·Regenerative Medicine·Cecilia Sahlgren, Urban Lendahl
May 2, 2014·Nature Reviews. Drug Discovery·Emma R Andersson, Urban Lendahl
Mar 26, 2014·Cell Research·Marika SjöqvistCecilia Sahlgren
Mar 6, 2013·Pharmacology & Therapeutics·Ingrid Espinoza, Lucio Miele
Sep 3, 2010·The Journal of Biological Chemistry·Nilay SethiYibin Kang
Nov 25, 2011·Cellular and Molecular Life Sciences : CMLS·Emma R Andersson
Jul 25, 2012·Cellular and Molecular Life Sciences : CMLS·Akiko MukaiSatoshi Goto
May 16, 2007·Médecine sciences : M/S·Julien ThérierMarc Billaud
Sep 12, 2006·Médecine sciences : M/S·Christel Brou, Frédérique Logeat
Sep 13, 2005·Molecular Membrane Biology·Marian B Wilkin, Martin Baron
Apr 16, 2010·Expert Opinion on Therapeutic Targets·Elodie Ristorcelli, Dominique Lombardo
Mar 26, 2010·Expert Opinion on Therapeutic Targets·Daoxin MaMing Hou
Feb 27, 2008·The Journal of Cell Biology·Thomas VaccariDavid Bilder
Mar 4, 2009·The Journal of Cell Biology·An-Chi TienHugo J Bellen
Nov 10, 2006·Critical Reviews in Biochemistry and Molecular Biology·David B Doroquez, Ilaria Rebay
Dec 21, 2005·The Journal of Investigative Dermatology. Symposium Proceedings·Brian J NickoloffJian-Zhong Qin

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Methods Mentioned

BETA
immunoprecipitation
pull-down
fluorescence microscopy
ubiquitination
confocal microscopy
immunoprecipitations
transfection

Software Mentioned

LSM

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