 Abstract
The spindle assembly checkpoint monitors sister chromatid bi-orientation in mitosis and prevents loss of sister chromatid cohesion in the presence of a demaged spindle. Mad2 and other proteins, such as Mad1 and Bub1, associate with kinetochores in prophase and prometaphase to monitor attachment of sister chromatids to the spindle.
The target of the spindle checkpoint is the anaphase-promoting complex (APC), a multi-subunit ubiquitin ligase, whose activity determines loss of sister chromatid cohesion and metaphase-anaphase transition. APC inhibition requires a direct interaction od Mad2 with Cdc20, a positive regulator of the APC. Mad2 also interacts with Mad1.
Cdc20 and Mad1 complexes with Mad2 are exclusive. The Mad2 binding sites on Mad1 and Cdc20 have been mapped using genetic and biochemical approaches. It has been shown that these unrelated proteins share an 10-residues Mad2 binding motif. This suggests that Mad2 is transferred from one ligand to the other via competition.
Selected references
| Luo X, Tang Z, Rizo J, Yu H | | The Mad2 spindle checkpoint protein undergoes similar major conformational
changes upon binding to either Mad1 or Cdc20. | | Mol Cell 2002 Jan;9(1) : 59-71. | | PMID: 11804586 |
| Musacchio A, Hardwick KG | | The spindle checkpoint: structural insights into dynamic signalling. | | Nat Rev Mol Cell Biol 2002 Oct;3(10) : 731-41. | | PMID: 12360190 |
This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.
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Biological Process |
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mitotic spindle checkpoint
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Cellular Component |
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nucleus |
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anaphase-promoting complex |
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Molecular Function |
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protein binding |
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