Human Mps1 kinase is required for the spindle assembly checkpoint but not for centrosome duplication.
Budding yeast Mps1p kinase has been implicated in both the duplication of microtubule-organizing centers and the spindle assembly checkpoint. Here we show that hMps1, the human homolog of yeast Mps1p, is a cell cycle-regulated kinase with maximal activity during M phase. hMps1 localizes to kinetochores and its activity and phosphorylation state increase upon activation of the mitotic checkpoint. By antibody microinjection and siRNA, we demonstrate that hMps1 is required for human cells to undergo checkpoint arrest in response to microtubule depolymerization. In contrast, centrosome (re-)duplication as well as cell division occur in the absence of hMps1. We conclude that hMps1 is required for the spindle assembly checkpoint but not for centrosome duplication.
Stucke
Volker M
VM
Max-Planck Institute for Biochemistry, Department of Cell Biology, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Silljé
Herman H W
HH
Arnaud
Lionel
L
Nigg
Erich A
EA
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000502:physiology*; D015870:Gene Expression; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D008938:Mitosis / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human