MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity Journal Article
| Authors: | Li, Y.; Gorbea, C.; Mahaffey, D.; Rechsteiner, M.; Benezra, R. |
| Article Title: | MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity |
| Abstract: | Cell cycle progression is monitored by checkpoint mechanisms that ensure faithful duplication and accurate segregation of the genome. Defects in spindle assembly or spindle-kinetochore attachment activate the mitotic checkpoint. Once activated, this checkpoint arrests cells prior to the metaphase-anaphase transition with unsegregated chromosomes, stable cyclin B, and elevated M phase promoting factor activity. However, the mechanisms underlying this process remain obscure. Here we report that upon activation of the mitotic checkpoint, MAD2, an essential component of the mitotic checkpoint, associates with the cyclin B-ubiquitin ligase, known as the cyclosome or anaphase-promoting complex. Moreover, purified MAD2 causes a metaphase arrest in cycling Xenopus laevis egg extracts and prevents cyclin B proteolysis by blocking its ubiquitination, indicating that MAD2 functions as an inhibitor of the cyclosome. Thus, MAD2 links the mitotic checkpoint pathway to the cyclin B destruction machinery which is critical in controlling the metaphase-anaphase transition. |
| Keywords: | controlled study; human cell; nonhuman; mitosis; animal cell; animals; cell cycle proteins; cell cycle; ubiquitin protein ligase; protein degradation; enzyme activity; hela cells; animalia; nuclear proteins; carrier proteins; anaphase; mitosis spindle; calcium-binding proteins; cyclin b; ubiquitin-protein ligases; metaphase; centromere; xenopus; xenopus laevis; ligases; mitotic checkpoint; fungal proteins; ubiquitin-protein ligase complexes; spindle assembly checkpoint; humans; human; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 94 |
| Issue: | 23 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1997-11-11 |
| Start Page: | 12431 |
| End Page: | 12436 |
| Language: | English |
| DOI: | 10.1073/pnas.94.23.12431 |
| PUBMED: | 9356466 |
| PROVIDER: | scopus |
| PMCID: | PMC24983 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
