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.
Mol Biol Cell
2009 May 01;209:2381-8. doi: 10.1091/mbc.e08-12-1206.
Show Gene links
Show Anatomy links
Oncogenic Adenomatous polyposis coli mutants impair the mitotic checkpoint through direct interaction with Mad2.
Zhang J
,
Neisa R
,
Mao Y
.
???displayArticle.abstract???
The majority of colorectal tumors are aneuploid because of the underlying chromosome instability (CIN) phenotype, in which a defective mitotic checkpoint is implicated. Adenomatous polyposis coli (APC), a tumor suppressor gene that is commonly mutated in colon cancers, has been suggested in causing CIN; however, the molecular mechanism remains unresolved. In this study, we report an interaction of tumor-associated N-terminal APC fragments (N-APC) with Mad2, an essential mitotic checkpoint protein, providing a direct molecular support for linking APC mutations to the generation of CIN. N-APC interacts with Mad2 in Xenopus egg extracts, colon cancer cells, and in vitro with purified components. The interaction between N-APC and Mad2 decreases the soluble pool of Mad2, which is essential for Mad2 cycling and releasing from unattached kinetochores to produce a diffusible |P;wait anaphase|P' signal. Addition of such an N-APC mutant of egg extracts inactivates the mitotic checkpoint. Expressing a tumor-associated N-APC mutant in mammalian cells with an intact mitotic checkpoint produces premature anaphase onset with missegregated chromosomes.
Abrieu,
CENP-E as an essential component of the mitotic checkpoint in vitro.
2000, Pubmed,
Xenbase
Abrieu,
CENP-E as an essential component of the mitotic checkpoint in vitro.
2000,
Pubmed
,
Xenbase
Bomont,
Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F.
2005,
Pubmed
Cahill,
Mutations of mitotic checkpoint genes in human cancers.
1998,
Pubmed
Chen,
BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1.
2002,
Pubmed
,
Xenbase
Chen,
Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores.
1996,
Pubmed
,
Xenbase
Chung,
Spindle checkpoint requires Mad1-bound and Mad1-free Mad2.
2002,
Pubmed
,
Xenbase
Cleveland,
Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling.
2003,
Pubmed
Cohen-Fix,
Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.
1996,
Pubmed
,
Xenbase
De Antoni,
The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint.
2005,
Pubmed
Draviam,
Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cells.
2006,
Pubmed
Fang,
Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex.
2002,
Pubmed
Fang,
Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1.
1998,
Pubmed
,
Xenbase
Fodde,
Mutations in the APC tumour suppressor gene cause chromosomal instability.
2001,
Pubmed
Gascoigne,
Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs.
2008,
Pubmed
Green,
Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC.
2003,
Pubmed
Green,
APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment.
2005,
Pubmed
Hoyt,
S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function.
1991,
Pubmed
Joslyn,
Dimer formation by an N-terminal coiled coil in the APC protein.
1993,
Pubmed
Kallio,
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.
1998,
Pubmed
Kaplan,
A role for the Adenomatous Polyposis Coli protein in chromosome segregation.
2001,
Pubmed
Kasai,
Prevalent loss of mitotic spindle checkpoint in adult T-cell leukemia confers resistance to microtubule inhibitors.
2002,
Pubmed
Kinzler,
Lessons from hereditary colorectal cancer.
1996,
Pubmed
Li,
Feedback control of mitosis in budding yeast.
1991,
Pubmed
Li,
Novel self-association of the APC molecule affects APC clusters and cell migration.
2008,
Pubmed
Luo,
The Mad2 spindle checkpoint protein has two distinct natively folded states.
2004,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nishisho,
Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
1991,
Pubmed
Putkey,
Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E.
2002,
Pubmed
Raff,
The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time.
2002,
Pubmed
Rowan,
APC mutations in sporadic colorectal tumors: A mutational "hotspot" and interdependence of the "two hits".
2000,
Pubmed
Shah,
Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing.
2004,
Pubmed
Su,
Association between wild type and mutant APC gene products.
1993,
Pubmed
Sudakin,
Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2.
2001,
Pubmed
Thompson,
Examining the link between chromosomal instability and aneuploidy in human cells.
2008,
Pubmed
Tighe,
Aneuploid colon cancer cells have a robust spindle checkpoint.
2001,
Pubmed
Tighe,
Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability.
2004,
Pubmed
,
Xenbase
Vink,
In vitro FRAP identifies the minimal requirements for Mad2 kinetochore dynamics.
2006,
Pubmed
Weaver,
Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss.
2003,
Pubmed
Weaver,
Does aneuploidy cause cancer?
2006,
Pubmed
Weiss,
The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint.
1996,
Pubmed
Zhang,
BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment.
2007,
Pubmed
,
Xenbase
Zou,
Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis.
1999,
Pubmed
,
Xenbase
Zur,
Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis.
2001,
Pubmed
