Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The spindle checkpoint prevents anaphase from occurring until all chromosomes have attached properly to the mitotic spindle. The checkpoint components Mad1 and Mad2 associate with unattached kinetochores and are probably involved in triggering the checkpoint. We now demonstrate that in Xenopus egg extracts Mad1 and Mad2 form a stable complex, whereas a fraction of Mad2 molecules is not bound to Mad1. The checkpoint establishment and maintenance are lost upon titrating out free Mad2 with an excess of Mad1 or a truncated Mad1 (amino acids 326-718, Mad1C) that contains the Mad2-binding region. Mad1N (amino acids 1-445) that binds kinetochores, but not Mad2, reduces Mad1 and Mad2 at kinetochores and abolishes checkpoint maintenance. Furthermore, the association between Mad2 and Cdc20, the activator for the anaphase-promoting complex, is enhanced under checkpoint-active condition compared with that at metaphase. Immunodepletion analysis shows that the Mad1-free Mad2 protein is unable to bind Cdc20, consistent with the model that kinetochore localization of Mad2 facilitates the formation of Mad2-Cdc20 complex. This study demonstrates that the ratio between Mad1 and Mad2 is critical for maintaining a pool of Mad1-free Mad2 that is necessary for the spindle checkpoint. We propose that Mad2 may become activated and dissociated from Mad1 at kinetochores and is replenished by the pool of Mad1-free Mad2.
Abrieu,
Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint.
2001, Pubmed,
Xenbase
Abrieu,
Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint.
2001,
Pubmed
,
Xenbase
Basu,
Mutations in the essential spindle checkpoint gene bub1 cause chromosome missegregation and fail to block apoptosis in Drosophila.
1999,
Pubmed
Chan,
Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC.
1999,
Pubmed
Chen,
Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores.
1998,
Pubmed
,
Xenbase
Chen,
The spindle checkpoint of budding yeast depends on a tight complex between the Mad1 and Mad2 proteins.
1999,
Pubmed
Chen,
Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores.
1996,
Pubmed
,
Xenbase
Fang,
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation.
1998,
Pubmed
,
Xenbase
Gardner,
The spindle checkpoint: two transitions, two pathways.
2000,
Pubmed
Gorbsky,
Protein dynamics at the kinetochore: cell cycle regulation of the metaphase to anaphase transition.
1999,
Pubmed
Hardwick,
Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast.
1995,
Pubmed
Hardwick,
Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption.
1996,
Pubmed
He,
The Schizosaccharomyces pombe spindle checkpoint protein mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex.
1997,
Pubmed
Hirano,
A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro.
1994,
Pubmed
,
Xenbase
Howell,
Visualization of Mad2 dynamics at kinetochores, along spindle fibers, and at spindle poles in living cells.
2000,
Pubmed
Hoyt,
Exit from mitosis: spindle pole power.
2000,
Pubmed
Hwang,
Budding yeast Cdc20: a target of the spindle checkpoint.
1998,
Pubmed
Jablonski,
The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis.
1998,
Pubmed
Jin,
Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1.
1998,
Pubmed
Kim,
Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint.
1998,
Pubmed
Li,
Mitotic forces control a cell-cycle checkpoint.
1995,
Pubmed
Li,
Identification of a human mitotic checkpoint gene: hsMAD2.
1996,
Pubmed
Lorca,
Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Minshull,
A MAP kinase-dependent spindle assembly checkpoint in Xenopus egg extracts.
1994,
Pubmed
,
Xenbase
Page,
The anaphase-promoting complex: new subunits and regulators.
1999,
Pubmed
Rieder,
The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores.
1995,
Pubmed
Shah,
Waiting for anaphase: Mad2 and the spindle assembly checkpoint.
2000,
Pubmed
Sharp-Baker,
Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity.
2001,
Pubmed
,
Xenbase
Sironi,
Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint.
2001,
Pubmed
,
Xenbase
Sudakin,
Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2.
2001,
Pubmed
Tang,
Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1.
2001,
Pubmed
,
Xenbase
Taylor,
The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase.
1998,
Pubmed
Taylor,
Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage.
1997,
Pubmed
Visintin,
CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
1997,
Pubmed
Waters,
Localization of Mad2 to kinetochores depends on microtubule attachment, not tension.
1998,
Pubmed
Weiss,
The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint.
1996,
Pubmed
Zhang,
Identification of an overlapping binding domain on Cdc20 for Mad2 and anaphase-promoting complex: model for spindle checkpoint regulation.
2001,
Pubmed
