PMID: 9637688Jun 24, 1998

The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation

Genes & Development
Guowei FangMarc Kirschner

Abstract

The spindle assembly checkpoint mechanism delays anaphase initiation until all chromosomes are aligned at the metaphase plate. Activation of the anaphase-promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from mitosis, and APC has been implicated as a target for the checkpoint intervention. We show that the human checkpoint protein hMAD2 prevents activation of APC by forming a hMAD2-CDC20-APC complex. When injected into Xenopus embryos, hMAD2 arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein exists in two-folded states: a tetramer and a monomer. Both the tetramer and the monomer bind to CDC20, but only the tetramer inhibits activation of APC and blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for inhibition, and a change in hMAD2 structure may play a role in transducing the checkpoint signal. There are at least three different forms of mitotic APC that can be detected in vivo: an inactive hMAD2-CDC20-APC ternary complex present at metaphase, a CDC20-APC binary complex active in degrading specific substrates at anaphase, and a CDH1-APC complex active later in mitosis and in G1. We conclude that the checkpoint-mediated cell cycle arrest involves hMAD2 receivin...Continue Reading

References

Aug 9, 1991·Cell·R Li, Andrew W Murray
Jan 10, 1991·Nature·M GlotzerMarc Kirschner
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·S Lahav-BaratzAvram Hershko
Nov 1, 1995·The Journal of Cell Biology·Kevin G Hardwick, Andrew W Murray
Feb 1, 1995·Current Opinion in Genetics & Development·Andrew W Murray
Dec 1, 1994·Current Opinion in Cell Biology·Andrew W Murray
Apr 1, 1996·The Journal of Cell Biology·A YamamotoD Koshland
Oct 11, 1996·Science·Y Li, R Benezra
Nov 15, 1996·Science·J M PetersMarc Kirschner
Dec 1, 1996·Current Opinion in Cell Biology·A D Rudner, Andrew W Murray
Jan 31, 1997·Science·R B Nicklas
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·X HeS Sazer
Aug 22, 1997·Cell·M SchwabW Seufert
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y LiR Benezra
Mar 7, 1998·Science·L H HwangAndrew W Murray

Citations

Oct 1, 1965·Journal of Cellular Physiology·A Korner
May 8, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A CiechanoverA L Schwartz
Jul 13, 2000·Cell Motility and the Cytoskeleton·M S CampbellG J Gorbsky
Jun 16, 2001·International Journal of Cancer. Journal International Du Cancer·Eva HernandoCarlos Cordón-Cardo
Jul 12, 2002·Cell Motility and the Cytoskeleton·Julie C CanmanGuowei Fang
Feb 19, 2000·Biochemical and Biophysical Research Communications·A OhtoshiM Hatakeyama
May 9, 2000·Biochemical and Biophysical Research Communications·Y YudkovskyAvram Hershko
Jan 1, 2014·Cancer Metastasis Reviews·Sarah DerksManon van Engeland
Mar 21, 2007·Journal of Biomedical Science·Rey-Huei Chen
Jun 3, 2004·Biochimica Et Biophysica Acta·Manuela Santarosa, Alan Ashworth
Jun 18, 2003·Biochemical and Biophysical Research Communications·Naihan XuDonald C Chang
Apr 25, 2003·Experimental and Molecular Pathology·Michael LinKathleen M Sakamoto
Oct 22, 2003·Archives of Medical Research·Carla Lopes, Claudio E Sunkel
Dec 11, 2002·Current Opinion in Cell Biology·Hongtao Yu
Jan 23, 1999·Current Opinion in Cell Biology·J M Peters
Dec 22, 1999·Current Opinion in Cell Biology·W Zachariae
Sep 19, 1998·Current Biology : CB·D A Wolf, P K Jackson
Sep 22, 2000·Trends in Cell Biology·P K JacksonJ D Reimann
Apr 27, 1999·Trends in Biochemical Sciences·K Nasmyth
Nov 26, 2010·Quarterly Reviews of Biophysics·David Barford
Jan 17, 2009·Chemical Reviews·Katherine WickliffeMichael Rape
Jan 27, 2004·Nature Cell Biology·Min Sup SongDae-Sik Lim
May 2, 2006·Nature Cell Biology·Michelle J HayesAndrew M Fry
Oct 5, 2011·Nature Cell Biology·Andrew W Murray
May 28, 2013·Nature Cell Biology·Weiping Wang, Marc Kirschner
Oct 1, 2005·Nature Reviews. Cancer·Geert J P L KopsD W Cleveland
Jan 23, 2010·Nature Reviews. Cancer·Juan-Manuel SchvartzmanR Benezra
Feb 18, 2011·Nature Reviews. Cancer·Huiling XuMichael J McKay
Aug 10, 2006·Nature Reviews. Molecular Cell Biology·Jan-Michael Peters
Apr 12, 2007·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, E D Salmon
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Kevin G Hardwick
Sep 26, 2012·Nature Structural & Molecular Biology·Kristina UzunovaJan-Michael Peters
Aug 3, 1999·European Journal of Biochemistry·K A Farr, O Cohen-Fix
Mar 10, 2001·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·S. A. Southern, C. S. Herrington
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Daisuke ItoTomohiro Matsumoto
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Andrea BallabeniMarc Kirschner
Jul 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sean D RyanBeth A A Weaver
May 15, 2002·Molecular Biology of the Cell·Eunah Chung, Rey-Huei Chen
Nov 17, 1999·Molecular Biology of the Cell·Holger BastiansJ V Ruderman
Aug 6, 1999·Molecular Biology of the Cell·R H ChenKevin G Hardwick
Jul 11, 2000·Molecular Biology of the Cell·J D LeversonT Hunter
Oct 22, 2002·Molecular Biology of the Cell·Katie B ShannonE D Salmon
Jul 23, 2004·Molecular Biology of the Cell·Suzanne VigneronT Lorca
Jan 12, 2007·Molecular Biology of the Cell·George WuYong Wan
Nov 29, 2002·The EMBO Journal·Toshiyuki HabuTomohiro Matsumoto
Dec 3, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·M YanagidaY Nakaseko
Dec 3, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Guowei FangMarc Kirschner
May 18, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Anna DeAntoniAndrea Musacchio
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·David Barford
Jun 17, 2004·Genes & Development·Jing Pan, Rey-Huei Chen
Mar 21, 2007·Genes & Development·Janet L Burton, Mark J Solomon
Oct 17, 2003·Genes & Development·Vincenzo D'AngiolellaDomenico Grieco
Jul 19, 2001·Genes & Development·J Chen, Guowei Fang
Sep 20, 2001·Genes & Development·C M PflegerMarc Kirschner
Apr 28, 2010·Molecular and Cellular Biology·Deyu LiJun-Yong Huang
Oct 13, 2010·Molecular and Cellular Biology·Johanna K AhlskogLea Sistonen
Jul 19, 2005·Molecular and Cellular Biology·Stefano CampanerIlan R Kirsch
Jun 29, 2000·Annual Review of Biochemistry·A M Page, P Hieter
Aug 12, 2009·BMC Infectious Diseases·Saira SarfrazAnwar A Siddiqui
Jul 26, 2007·Cell Division·Laura A Diaz-Martinez, Hongtao Yu
Jan 21, 2009·Cell Division·Min Li, Pumin Zhang
Apr 9, 2009·Journal of Cell Science·Chang-Young JangGuowei Fang
May 8, 2009·Cell Structure and Function·Yujian LuHeng Liu
May 7, 1999·Environmental Health Perspectives·R E ShackelfordR S Paules
Feb 7, 2008·PloS One·Bashar IbrahimPeter Dittrich
Oct 11, 2012·PloS One·Denis OstapenkoMark J Solomon
Dec 5, 2012·ISRN Oncology·Josep J Centelles
Mar 13, 2009·Reproduction : the Official Journal of the Society for the Study of Fertility·Zuzanna MaciejewskaMaria A Ciemerych
Feb 5, 2014·Clinical & Experimental Metastasis·Hassan Fazilaty, Parvin Mehdipour
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ilana BraunsteinAvram Hershko
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·D C FarruggioJ V Ruderman
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·Katja Wassmann, R Benezra
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·L S MichelR Benezra
Mar 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·G PoelzlM E Mendelsohn
Jul 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michel V HadjihannasJürgen Behrens
Jan 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xingxu HuangPumin Zhang
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y C LiuS M Weissman
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·M A WetermanA G van Kessel
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·D A SkoufiasR L Margolis
Mar 19, 2013·Annual Review of Biochemistry·Leonardo K Teixeira, Steven I Reed
Dec 30, 2004·Proceedings of the National Academy of Sciences of the United States of America·Baoying LiuChou-Zen Giam
Sep 25, 2012·Cellular and Molecular Life Sciences : CMLS·Verónica ParrillasMario Mellado
Mar 11, 1999·Current Opinion in Genetics & Development·A Amon
Sep 26, 2012·The Journal of Cell Biology·Daisuke Izawa, J Pines
Sep 1, 2005·The Journal of Cell Biology·Oi Kwan Wong, Guowei Fang
Oct 23, 2014·International Journal of Molecular Sciences·Bashar Ibrahim, Richard Henze
Apr 13, 2005·The Journal of Cell Biology·Jessica B CasalettoSally Kornbluth
Apr 13, 2005·The Journal of Cell Biology·Geert J P L KopsD W Cleveland
Mar 8, 2000·The Journal of Cell Biology·Kevin G HardwickAndrew W Murray
Dec 15, 2010·The Journal of Cell Biology·Sang Hyun LeeHideyuki Saya
Feb 16, 2006·The Journal of Cell Biology·Darren J BakerJ M van Deursen
Oct 24, 1998·The Journal of Cell Biology·R H ChenAndrew W Murray
Jun 11, 2008·The Journal of Cell Biology·Anthony TigheStephen S Taylor
Apr 2, 2008·The Journal of Cell Biology·Akiko SekiGuowei Fang
Jan 4, 2001·Drug Metabolism Reviews·P M Flatt, J A Pietenpol
Jun 28, 2000·The Journal of Cell Biology·A D RudnerAndrew W Murray
Jun 26, 2002·The Journal of Cell Biology·Jordan W RaffJun-Yong Huang
Sep 6, 2001·The Journal of Cell Biology·M A Hoyt
Apr 1, 2015·The Journal of Cell Biology·Devinderjit K MoudgilGordon K Chan
Jun 28, 2000·The Journal of Cell Biology·A D Rudner, Andrew W Murray
Apr 4, 2001·The Journal of Cell Biology·N den Elzen, J Pines
Jan 26, 2011·Critical Reviews in Biochemistry and Molecular Biology·Janel R McLeanKathleen L Gould
Apr 8, 2015·Pharmacology & Therapeutics·Lixia WangWenyi Wei
Mar 29, 2011·Seminars in Cell & Developmental Biology·Soonjoung Kim, Hongtao Yu
Feb 2, 2010·Biochemical and Biophysical Research Communications·Chang-Young JangGuowei Fang
Dec 26, 2009·Experimental and Molecular Pathology·Qingdu LiuQiang Wang
Jun 12, 2008·Biochimica Et Biophysica Acta·Renske van LeukenRob Wolthuis
May 13, 2008·Biochimica Et Biophysica Acta·Saskia J E Suijkerbuijk, Geert J P L Kops
Oct 9, 2007·Current Opinion in Structural Biology·Marina Mapelli, Andrea Musacchio
Jan 8, 2008·Molecular and Cellular Endocrinology·Jacek Z KubiakMaria A Ciemerych
Dec 11, 2007·Biochimica Et Biophysica Acta·Barbara T McGroganAmanda McCann
Aug 3, 2007·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Mathias Schmidt, Holger Bastians
May 16, 2015·Computational and Structural Biotechnology Journal·Bashar Ibrahim
Nov 19, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Takayuki HattoriM Kitagawa
Jun 20, 2003·Cell Proliferation·Katrien VermeulenZwi N Berneman
Jan 6, 2009·Journal of Cellular and Molecular Medicine·Wei WangXuedong Liu
Jun 5, 2003·Clinical Endocrinology·Chris J McCabe, Anthony P Heaney
Jan 10, 2009·Biotechnology and Bioengineering·Salim CharaniyaWei-Shou Hu
Mar 10, 2006·The EMBO Journal·Marina MapelliAndrea Musacchio
Nov 3, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jakob Nilsson
Jul 21, 2011·The EMBO Journal·Luca L FavaAnna Santamaria
Jun 15, 2011·The EMBO Journal·Michael OrthOlaf Stemmann
Mar 10, 2011·International Journal of Cancer. Journal International Du Cancer·Martina BirkMathias Schmidt
Nov 30, 2004·Gene Expression Patterns : GEP·Stephanie A PangasAleksandar Rajkovic
Apr 22, 2015·Cell Cycle·Zemfira N KaramyshevaHongtao Yu
Oct 19, 2006·Current Opinion in Cell Biology·Beth A A Weaver, D W Cleveland
Apr 8, 2006·Experimental Cell Research·James DavenportRakesh Goorha
Oct 11, 2005·Trends in Cell Biology·Gordon K ChanTim Yen
Oct 18, 2005·Current Opinion in Cell Biology·Darren J BakerJ M van Deursen
Apr 9, 2011·Biochemical and Biophysical Research Communications·Chang-Young JangGuowei Fang
Mar 8, 2013·Biochimica Et Biophysica Acta·Florian BassermannMichele Pagano
May 30, 2015·Molecular Biology of the Cell·Nathaniel I KrefmanGeorjana Barnes
Nov 18, 2003·Annual Review of Genetics·Daniel J Lew, Daniel J Burke
May 14, 1999·Current Opinion in Genetics & Development·K W DobieG H Karpen
Mar 1, 2000·Experimental Cell Research·T ListovskyM Brandeis
Nov 4, 2000·Cell Proliferation·M Molinari
Apr 30, 2014·Cell Cycle·Yanchang WangKelly McKnight
Jan 31, 2002·Current Biology : CB·Ann B GeorgiMarc Kirschner
Feb 2, 1999·Experimental Cell Research·J M CraigP Vagnarelli
Feb 23, 2005·Current Biology : CB·Kevin G Hardwick
Sep 19, 2003·Current Biology : CB·Katja WassmannBernard Maro
Feb 8, 2005·Current Biology : CB·Anna De AntoniAndrea Musacchio
Nov 24, 2012·Current Biology : CB·Pablo Lara-GonzalezStephen S Taylor
Jun 9, 2004·Current Biology : CB·Bonnie J HowellE D Salmon
May 1, 1999·Experimental Cell Research·J M Peters
Nov 24, 2001·Current Biology : CB·C HendricksonS L Holloway
Nov 11, 2008·Molecular Cell·Jungseog KangHongtao Yu
Dec 27, 2006·Cancer Cell·Rocío SotilloR Benezra
May 24, 2001·Cell·P V JallepalliC Lengauer
Mar 31, 2005·Cell·K Nasmyth
Nov 21, 2007·Cell·Maojun YangXuelian Luo
Jan 28, 2004·Cell·Andrew W Murray
Jul 4, 2008·Journal of Molecular Biology·Maggie K L FungXianghong Wang
Dec 24, 2014·Biochemical and Biophysical Research Communications·Xianghua ZhangChang-Young Jang
Nov 13, 2008·Structure·Xuelian Luo, Hongtao Yu
May 18, 2011·Biochemical and Biophysical Research Communications·Jennifer A Keller, E M Petty
Jan 16, 2009·PLoS Biology·Marco SimonettaAndrea Ciliberto
May 23, 2003·Cold Spring Harbor Symposia on Quantitative Biology·M Dobles, P K Sorger
Aug 30, 2008·Biology of Reproduction·Anna HupalowskaMaria A Ciemerych
Mar 7, 2001·Current Biology : CB·M S SchwabJ L Maller
Jul 27, 2014·Biochemical and Biophysical Research Communications·Youguo LingQuanbin Xu
May 23, 2009·American Journal of Clinical Pathology·Li WangDaiming Fan
Nov 7, 2000·Genes, Chromosomes & Cancer·M J PercyE M Petty
Jul 25, 2017·International Journal of Molecular Sciences·Jin-Mei Cheng, Yi-Xun Liu
Mar 2, 2018·International Journal of Molecular Sciences·Jaroslav KalousAndrej Susor
Mar 24, 2018·Cell Division·Anita E Raposo, Sabine C Piller
Jul 12, 2003·Nature Cell Biology·Eunah Chung, Rey-Huei Chen
Mar 3, 2004·Nature Biotechnology·Joshua T JonesTobias Meyer
May 13, 1999·The Journal of Biological Chemistry·R GrossbergerJ M Peters
Mar 22, 2002·Nature Reviews. Cancer·P V Jallepalli, C Lengauer
Mar 17, 2004·Nature Structural & Molecular Biology·Xuelian LuoHongtao Yu
Feb 12, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Vanessa L Horner, Mariana F Wolfner
Jul 25, 2009·The EMBO Journal·Andrea Ciliberto, Jagesh V Shah
Aug 13, 2005·Molecular Reproduction and Development·Norihiko NakamuraYasuhiro Iwao
Jan 9, 2001·Nature Cell Biology·M PeterJ C Labbé
Nov 13, 1999·Nature Cell Biology·P Clute, J Pines
Nov 13, 1999·Nature Cell Biology·D O Morgan
Jan 18, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Po-Yuan KeZee-Fen Chang
Mar 23, 2012·Nature·William C H ChaoDavid Barford
May 19, 2019·The Journal of Biological Chemistry·Saratchandra Singh KhumukchamBramanandam Manavathi
Dec 5, 2013·The Journal of Biological Chemistry·Ryo KikuchiMikihiko Naito
Jul 16, 2014·The EMBO Journal·Laura A Diaz-MartinezHongtao Yu
Mar 28, 2002·Physiological Reviews·Michael H Glickman, A Ciechanover
Mar 14, 2002·The Journal of Biological Chemistry·Abolfazl AsadiAnders Jacobsson
Feb 1, 2003·The Journal of Biological Chemistry·Yuan ZhouDong-Yan Jin
Mar 17, 2004·Oncogene·Rajnish Bharadwaj, Hongtao Yu
Dec 23, 2003·The Journal of Biological Chemistry·Shinobu HondaHideyuki Saya
Apr 20, 2005·Oncogene·Marcel A T M van Vugt, René H Medema
Jul 3, 2007·The Journal of Biological Chemistry·Andrew J HollandStephen S Taylor
Jul 3, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wenqi LiYong Wan
Nov 1, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M J KallioJ E Eriksson
Jul 25, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Inbal Ben-EliezerNava Dekel
Jul 17, 2003·The Journal of Biological Chemistry·Donald C ChangKathy Q Luo
Dec 14, 2004·Journal of Biomedical Science·Karen Man-Fong SzeIrene Oi-Lin Ng
Sep 13, 2006·The Journal of Cell Biology·Suzanne MadgwickKeith T Jones
Dec 17, 2014·The Journal of Biological Chemistry·Laura A Diaz-MartinezHongtao Yu
Aug 25, 1999·The Journal of Cell Biology·S KotaniK Todokoro
Jan 1, 2016·AIMS Molecular Science·Song-Tao Liu, Hang Zhang
Nov 24, 1999·Journal of Cellular Physiology·D Kornitzer, A Ciechanover
Mar 23, 2007·The Journal of Biological Chemistry·Akiko Seki, Guowei Fang
Jul 22, 2006·Biochemical Society Transactions·K B Jeganathan, J M van Deursen
Jun 2, 2007·Molecular and Cellular Biochemistry·Li LiKeke Huo
Jun 15, 2020·Journal of Molecular Neuroscience : MN·Yuduo GuoChunjiang Yu
Oct 13, 2001·The Journal of Biological Chemistry·J Bembenek, H Yu
Sep 17, 1999·The Journal of Biological Chemistry·N SugataK Todokoro
Jan 5, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G J GorbskyL M Topper
Jun 6, 2018·Frontiers in Cell and Developmental Biology·Yibo LuoSong-Tao Liu
Jan 25, 2019·The Journal of Cell Biology·Tatiana Alfonso-PérezFrancis A Barr
Apr 3, 2004·Cancer Research·Tamotsu SudoNaoto T Ueno
Jul 29, 2004·The Journal of Biological Chemistry·Masuo Goto, Edward M Eddy

Related Concepts

SMAD2 protein, human
Smad2 protein, Xenopus
CDC20 protein, S cerevisiae
Anaphase
Biopolymers
Cell-Free System
DNA Helix Destabilizing Proteins
Embryonic Structures, Nonmammalian
HeLa Cells
Ligase

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