Mad2 phosphorylation regulates its association with Mad1 and the APC/C Journal Article

   


Authors: Wassmann, K.; Liberal, V.; Benezra, R.
Article Title: Mad2 phosphorylation regulates its association with Mad1 and the APC/C
Abstract: Improper attachment of the mitotic spindle to the kinetochores of paired sister chromatids in mitosis is monitored by a checkpoint that leads to an arrest in early metaphase. This arrest requires the inhibitory association of Mad2 with the anaphase promoting complex/cyclosome (APC/C). It is not known how the association of Mad2 with the kinetochore and the APC/C is regulated in mitosis. Here, we demonstrate that human Mad2 is modified through phosphorylation on multiple serine residues in vivo in a cell cycle dependent manner and that only unphosphorylated Mad2 interacts with Mad1 or the APC/C in vivo. A Mad2 mutant containing serine to aspartic acid mutations mimicking the C-terminal phosphorylation events fails to interact with Mad1 or the APC/C and acts as a dominant-negative antagonist of wild-type Mad2. These data suggest that the phosphorylation state of Mad2 regulates its checkpoint activity by modulating its association with Mad1 and the APC/C.
Keywords: controlled study; protein phosphorylation; human cell; mutation; antineoplastic agents; cell cycle proteins; cell cycle; sister chromatid; serine; carboxy terminal sequence; protein protein interaction; in vivo study; hela cells; phosphorylation; nuclear proteins; regulatory mechanism; carrier proteins; phosphoproteins; mitosis spindle; calcium-binding proteins; repressor proteins; aspartic acid; centromere; nocodazole; ligases; mitotic checkpoint; fungal proteins; protein mad2; mitosis inhibition; anaphase promoting complex; ubiquitin-protein ligase complexes; protein mad1; mad2; metaphase arrest; humans; human; priority journal; article; anaphase promoting complex-cyclosome
Journal Title: EMBO Journal
Volume: 22
Issue: 4
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2003-02-17
Start Page: 797
End Page: 806
Language: English
DOI: 10.1093/emboj/cdg071
PUBMED: 12574116
PROVIDER: scopus
PMCID: PMC145433
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0037450643&partnerID=40&md5=79dc106c084fa72642af7f454580527c
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Katharina Wassmann
    3 Wassmann
  2. Robert Benezra
    146 Benezra
  3. Vasco Liberal
    4 Liberal
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