Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Anna DeAntoniAndrea Musacchio


Mad2 is an essential component of the spindle assembly checkpoint (SAC), a molecular device designed to coordinate anaphase onset with the completion of chromosome attachment to the spindle. Capture of chromosome by microtubules occur on protein scaffolds known as kinetochores. The SAC proteins are recruited to kinetochores in prometaphase where they generate a signal that halts anaphase until all sister chromatid pairs are bipolarly oriented. Mad2 is a subunit of the mitotic checkpoint complex, which is regarded as the effector of the spindle checkpoint. Its function is the sequestration of Cdc20, a protein required for progression into anaphase. The function of Mad2 in the checkpoint correlates with a dramatic conformational rearrangement of the Mad2 protein. Mad2 adopts a closed conformation (C-Mad2) when bound to Cdc20, and an open conformation (O-Mad2) when unbound to this ligand. Checkpoint activation promotes the conversion of O-Mad2 to Cdc20-bound C-Mad2. We show that this conversion requires a C-Mad2 template and we identify this in Mad1-bound Mad2. In our proposition, Mad1-bound C-Mad2 recruits O-Mad2 to kinetochores, stimulating Cdc20 capture, implying that O-Mad2 and C-Mad2 form dimers. We discuss Mad2 oligomerizati...Continue Reading


Aug 9, 1991·Cell·R Li, A W Murray
Mar 7, 1998·Science·L H HwangA W Murray
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·Katja Wassmann, R Benezra
Oct 24, 1998·The Journal of Cell Biology·R H ChenA W Murray
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·M Ruhlen
Aug 6, 1999·Molecular Biology of the Cell·R H ChenKevin G Hardwick
Mar 4, 2000·Nature Structural Biology·Xuelian LuoG Wagner
May 15, 2002·Molecular Biology of the Cell·Eunah Chung, Rey-Huei Chen
Jun 7, 2002·Molecular Cell·Jan-Michael Peters
Aug 28, 2002·The Journal of Cell Biology·Marko J KallioGary J Gorbsky
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Kevin G Hardwick
Oct 22, 2002·Molecular Biology of the Cell·Katie B ShannonEdward D Salmon
Nov 29, 2002·The EMBO Journal·Toshiyuki HabuTomohiro Matsumoto
Dec 24, 2003·The Journal of Cell Biology·Brian J TunquistJames L Maller
Mar 17, 2004·Oncogene·Rajnish Bharadwaj, Hongtao Yu
Mar 17, 2004·Nature Structural & Molecular Biology·Xuelian LuoHongtao Yu
Jun 9, 2004·Current Biology : CB·Bonnie J HowellEdward D Salmon
Jul 9, 2004·Developmental Cell·Patrick MeraldiPeter K Sorger
Feb 8, 2005·Current Biology : CB·Anna De AntoniAndrea Musacchio


Oct 5, 2011·Cell and Tissue Research·Pavla KarabinovaAndrej Susor
May 4, 2012·Molecular Biology of the Cell·Friederike AlthoffChristian F Lehner
Mar 11, 2009·Nucleic Acids Research·Taraswi BanerjeeSusanta Roychoudhury
May 18, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Mitsuhiro Yanagida
Apr 28, 2010·Molecular and Cellular Biology·Deyu LiJun-Yong Huang
Jan 16, 2009·PLoS Biology·Marco SimonettaAndrea Ciliberto
Feb 7, 2008·PloS One·Bashar IbrahimPeter Dittrich
Oct 27, 2006·Proceedings of the National Academy of Sciences of the United States of America·Richard P Sear, Martin Howard
Dec 26, 2009·Experimental and Molecular Pathology·Qingdu LiuQiang Wang
Oct 9, 2007·Current Opinion in Structural Biology·Marina Mapelli, Andrea Musacchio
Dec 11, 2007·Biochimica Et Biophysica Acta·Barbara T McGroganAmanda McCann
Jul 14, 2012·Journal of Molecular Biology·Jonathan P B LeesR Blake Hill
Feb 8, 2005·Current Biology : CB·Anna De AntoniAndrea Musacchio
Mar 10, 2006·The EMBO Journal·Marina MapelliAndrea Musacchio
Jun 26, 2020·Nature·Chikashi TeraoYoichiro Kamatani

Related Concepts

CDC20 protein, human
MAD2L1 protein, human
Calcium-Binding Proteins
Meiotic Spindle Apparatus
Protein Conformation
Repressor Molecules
Cell Cycle Proteins
Genes, cdc
Chromosome Segregation

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.