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.
Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage
The Schizosaccharomyces pombe spindle checkpoint protein mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex
Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1
Microinjection of antibody to Mad2 protein into mammalian cells in mitosis induces premature anaphase
Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation
The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase
Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1
The HORMA domain: a common structural denominator in mitotic checkpoints, chromosome synapsis and DNA repair
The spindle checkpoint of budding yeast depends on a tight complex between the Mad1 and Mad2 proteins
Visualization of Mad2 dynamics at kinetochores, along spindle fibers, and at spindle poles in living cells
Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint
Identification of an overlapping binding domain on Cdc20 for Mad2 and anaphase-promoting complex: model for spindle checkpoint regulation
The awesome power of multiple model systems: interpreting the complex nature of spindle checkpoint signaling
miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression
Partial downregulation of MAD1 causes spindle checkpoint inactivation and aneuploidy, but does not confer resistance towards taxol
MAD2DeltaC induces aneuploidy and promotes anchorage-independent growth in human prostate epithelial cells
Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons
Requirements for protein phosphorylation and the kinase activity of polo-like kinase 1 (Plk1) for the kinetochore function of mitotic arrest deficiency protein 1 (Mad1)
Mad2-independent spindle assembly checkpoint activation and controlled metaphase-anaphase transition in Drosophila S2 cells
Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a 'safety belt' binding mechanism for the spindle checkpoint
Intra-oocyte localization of MAD2 and its relationship with kinetochores, microtubules, and chromosomes in rat oocytes during meiosis
Changing Mad2 levels affects chromosome segregation and spindle assembly checkpoint control in female mouse meiosis I
The ARF tumor suppressor prevents chromosomal instability and ensures mitotic checkpoint fidelity through regulation of Aurora B
The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint
Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine
Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest
Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction
Accumulation of Mad2-Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae
Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent
Mad2 binding is not sufficient for complete Cdc20 sequestering in mitotic transition control (an in silico study)
MAD1L1 Arg558His and MAD2L1 Leu84Met interaction with smoking increase the risk of colorectal cancer
Conformation-specific binding of p31(comet) antagonizes the function of Mad2 in the spindle checkpoint
The histone deacetylase inhibitor LBH589 inhibits expression of mitotic genes causing G2/M arrest and cell death in head and neck squamous cell carcinoma cell lines
Identification of distinct and common gene expression changes after oxidative stress and gamma and ultraviolet radiation
Spindle assembly checkpoint gene mdf-1 regulates germ cell proliferation in response to nutrition signals in C. elegans
A Golgi-localized pool of the mitotic checkpoint component Mad1 controls integrin secretion and cell migration
Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos
Mad2 Inhibitor-1 (M2I-1): A Small Molecule Protein-Protein Interaction Inhibitor Targeting the Mitotic Spindle Assembly Checkpoint
Role of the Mad2 dimerization interface in the spindle assembly checkpoint independent of kinetochores
Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing
The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20
Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding
Catalytic assembly of the mitotic checkpoint inhibitor BubR1-Cdc20 by a Mad2-induced functional switch in Cdc20
The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation
Absence of a conventional spindle mitotic checkpoint in the binucleated single-celled parasite Giardia intestinalis
Conformational dynamics of the Hop1 HORMA domain reveal a common mechanism with the spindle checkpoint protein Mad2
Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores
Phosphorylation regulates the p31Comet-mitotic arrest-deficient 2 (Mad2) interaction to promote spindle assembly checkpoint (SAC) activity
Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population
Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex
BubR1 Is Essential for Thio-Dimethylarsinic Acid-Induced Spindle Assembly Checkpoint and Mitotic Cell Death for Preventing the Accumulation of Abnormal Cells
Direct interactions of mitotic arrest deficient 1 (MAD1) domains with each other and MAD2 conformers are required for mitotic checkpoint signaling
Characterization of regions in hsMAD1 needed for binding hsMAD2. A polymorphic change in an hsMAD1 leucine zipper affects MAD1-MAD2 interaction and spindle checkpoint function
Transcriptional abnormality of the hsMAD2 mitotic checkpoint gene is a potential link to hepatocellular carcinogenesis
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