Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint

The EMBO Journal
Lucia SironiAndrea Musacchio

Abstract

Mad2 is a key component of the spindle checkpoint, a device that controls the fidelity of chromosome segregation in mitosis. The ability of Mad2 to form oligomers in vitro has been correlated with its ability to block the cell cycle upon injection into Xenopus embryos. Here we show that Mad2 forms incompatible complexes with Mad1 and Cdc20, neither of which requires Mad2 oligomerization. A monomeric point mutant of Mad2 can sustain a cell cycle arrest of comparable strength to that of the wild-type protein. We show that the interaction of Mad2 with Mad1 is crucial for the localization of Mad2 to kinetochores, where Mad2 interacts with Cdc20. We propose a model that features the kinetochore as a 'folding factory' for the formation of a Mad2-Cdc20 complex endowed with inhibitory activity on the anaphase promoting complex.

References

Aug 9, 1991·Cell·R Li, Andrew W Murray
Nov 1, 1995·The Journal of Cell Biology·Kevin G Hardwick, Andrew W Murray
Oct 11, 1996·Science·Y Li, Robert Benezra
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·X HeS Sazer
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y LiRobert Benezra
Feb 4, 1998·Trends in Genetics : TIG·Kevin G Hardwick
Mar 7, 1998·Science·L H HwangAndrew W Murray
Jun 12, 1998·The Journal of Cell Biology·J C WatersEdward D Salmon
Jun 12, 1998·The Journal of Cell Biology·G J GorbskyAndrew W Murray
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·Katja Wassmann, Robert Benezra
Oct 24, 1998·The Journal of Cell Biology·R H ChenAndrew W Murray
Jan 1, 1999·Nature·C LengauerB Vogelstein
Mar 11, 1999·Current Opinion in Genetics & Development·A Amon
Apr 13, 1999·Biochemical and Biophysical Research Communications·T W SeeleyJ Y Zhen
Aug 6, 1999·Molecular Biology of the Cell·R H ChenKevin G Hardwick
Aug 31, 1999·Genes & Development·W Zachariae, Kim Nasmyth
Mar 4, 2000·Nature Structural Biology·Xuelian LuoG Wagner
Feb 13, 2001·Cell·J V Shah, Don W Cleveland
Jul 19, 2001·Genes & Development·J Chen, Guowei Fang

Citations

Jul 12, 2002·Cell Motility and the Cytoskeleton·Julie C CanmanGuowei Fang
Apr 10, 2007·Nature Cell Biology·Eulalie BuffinRoger E Karess
Oct 29, 2013·Nature Cell Biology·Stephanie HeinrichSilke Hauf
Aug 10, 2006·Nature Reviews. Molecular Cell Biology·Jan-Michael Peters
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Kevin G Hardwick
Jul 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sean D RyanBeth A Weaver
May 15, 2002·Molecular Biology of the Cell·Eunah Chung, Rey-Huei Chen
Oct 22, 2002·Molecular Biology of the Cell·Katie B ShannonEdward D Salmon
Nov 29, 2002·The EMBO Journal·Toshiyuki HabuTomohiro Matsumoto
May 18, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Anna DeAntoniAndrea Musacchio
Jan 16, 2009·PLoS Biology·Marco SimonettaAndrea Ciliberto
Feb 7, 2008·PloS One·Bashar IbrahimPeter Dittrich
Dec 24, 2003·The Journal of Cell Biology·Brian J TunquistJames L Maller
Oct 22, 2008·The Journal of Cell Biology·Takaharu G YamamotoRisa Kitagawa
Jan 26, 2011·Critical Reviews in Biochemistry and Molecular Biology·Janel R McLeanKathleen L Gould
Jan 3, 2012·Current Opinion in Cell Biology·Jonas F Dorn, Paul S Maddox
Feb 15, 2007·Reproductive Biomedicine Online·Stéphan GascaSamir Hamamah
Dec 26, 2009·Experimental and Molecular Pathology·Qingdu LiuQiang Wang
Oct 21, 2015·Current Biology : CB·Andrea Musacchio
May 27, 2008·Toxicology and Applied Pharmacology·Samuel C McNeelyJ Christopher States
Oct 9, 2007·Current Opinion in Structural Biology·Marina Mapelli, Andrea Musacchio
Dec 11, 2007·Biochimica Et Biophysica Acta·Barbara T McGroganAmanda McCann
Nov 25, 2015·The Journal of Cell Biology·Scott C Rosenberg, Kevin D Corbett
May 11, 2004·EMBO Reports·Peter SteensgaardAndrea Musacchio
Mar 10, 2006·The EMBO Journal·Marina MapelliAndrea Musacchio
Jun 15, 2011·The EMBO Journal·Michael OrthOlaf Stemmann
Jun 11, 2002·Biochemical and Biophysical Research Communications·Yuan ZhouDong-Yan Jin
Oct 11, 2005·Trends in Cell Biology·Gordon K ChanTim Yen
Nov 18, 2003·Annual Review of Genetics·Daniel J Lew, Daniel J Burke
May 12, 2015·Nature Cell Biology·Martin HoulardKim Nasmyth
Mar 17, 2015·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Lénaïg DéfachellesRoger E Karess
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
Apr 25, 2006·Current Biology : CB·Martin VinkAndrea Musacchio
Jan 3, 2012·Current Biology : CB·Derek T C Lau, Andrew W Murray
Jul 9, 2004·Developmental Cell·Patrick MeraldiPeter K Sorger
Jun 7, 2002·Molecular Cell·Jan-Michael Peters
Mar 31, 2005·Cell·Kim Nasmyth
Nov 21, 2007·Cell·Maojun YangXuelian Luo
Nov 13, 2008·Structure·Xuelian Luo, Hongtao Yu
Oct 18, 2014·Frontiers in Physiology·Semin Lee, Victor M Bolanos-Garcia
Jan 20, 2017·Nature·Alex C FaesenAndrea Musacchio
Mar 17, 2004·Nature Structural & Molecular Biology·Xuelian LuoHongtao Yu
Aug 4, 2007·Virchows Archiv : an International Journal of Pathology·Mitsuhiko OsakiHisao Ito
Mar 23, 2012·Nature·William C H ChaoDavid Barford
Jul 23, 2020·Molecular Biology of the Cell·Lénaïg DéfachellesNeedhi Bhalla
Apr 6, 2019·Nature Communications·Jun WanBeth A Weaver
Jul 11, 2019·Nucleic Acids Research·Fengjie YuanYing Zhao
Feb 13, 2020·F1000Research·Angela Flavia Serpico, Domenico Grieco
Jan 1, 2016·AIMS Molecular Science·Song-Tao Liu, Hang Zhang

Related Concepts

MAD1 protein, S cerevisiae
MAD1L1 protein, human
Mad1l1 protein, mouse
CDC20 protein, S cerevisiae
MAD2 protein, S cerevisiae
Mad2l1 protein, mouse
Mad2l2 protein, mouse
Anaphase
Monoclonal Antibodies
Calcium-Binding Proteins

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.