Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint.
The mitotic checkpoint acts to inhibit entry into anaphase until all chromosomes have successfully attached to spindle microtubules. Unattached kinetochores are believed to release an activated form of Mad2 that inhibits APC/C-dependent ubiquitination and subsequent proteolysis of components needed for anaphase onset. Using Xenopus egg extracts, a vertebrate homolog of yeast Mps1p is shown here to be a kinetochore-associated kinase, whose activity is necessary to establish and maintain the checkpoint. Since high levels of Mad2 overcome checkpoint loss in Mps1-depleted extracts, Mps1 acts upstream of Mad2-mediated inhibition of APC/C. Mps1 is essential for the checkpoint because it is required for recruitment and retention of active CENP-E at kinetochores, which in turn is necessary for kinetochore association of Mad1 and Mad2.
Abrieu
A
A
Ludwig Institute for Cancer Research, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Magnaghi-Jaulin
L
L
Kahana
J A
JA
Peter
M
M
Castro
A
A
Vigneron
S
S
Lorca
T
T
Cleveland
D W
DW
Labbé
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008297:Male; D008540:Meiosis; D008677:Metaphase; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D013094:Spermatozoa / Q000502:physiology; D014452:Ubiquitins / Q000378:metabolism; D014714:Vertebrates; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
C534699:CCNB1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D056744:Cyclin B1; D005656:Fungal Proteins; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D029867:Xenopus Proteins; C068688:centromere protein E; D011494:Protein Kinases; C102333:histone H1 kinase; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C514980:RPS27 protein, Xenopus; C075840:TTK protein, human; C093416:MPS1 protein, S cerevisiae; D015739:Nocodazole