title: Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe.
abstract: The spindle assembly checkpoint pathway is not essential for normal mitosis but ensures accurate nuclear division by blocking the metaphase to anaphase transition in response to a defective spindle. Here, we report the isolation of a new spindle checkpoint gene, mph1 (Mps1p-like pombe homolog), in the fission yeast Schizosaccharomyces pombe, that is required for checkpoint activation in response to spindle defects. mph1 functions upstream of mad2, a previously characterized component of the spindle checkpoint. Overexpression of mph1, like overexpression of mad2, mimics activation of the checkpoint and imposes a metaphase arrest. mph1 protein shares sequence similarity with Mps1p, a dual specificity kinase that functions in the spindle checkpoint of the budding yeast Saccharomyces cerevisiae. Complementation analysis demonstrates that mph1 and Mps1p are functionally related. They differ in that Mps1p, but not mph1, has an additional essential role in spindle pole body duplication. We propose that mph1 is the MPS1 equivalent in the spindle checkpoint pathway but not in the SPB duplication pathway. Overexpression of mad2 does not require mph1 to impose a metaphase arrest, which indicates a mechanism of spindle checkpoint activation other than mph1/Mps1p kinase-dependent phosphorylation. In the same screen which led to the isolation of mad2 and mph1, we also isolated dph1, a cDNA that encodes a protein 46% identical to an S. cerevisiae SPB duplication protein, Dsk2p. Our initial characterization indicates that S.p. dph1 and S.c. DSK2 are functionally similar. Together these results suggest that the budding and fission yeasts share common elements for SPB duplication, despite differences in SPB structure and the timing of SPB duplication relative to mitotic entry.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: M H
authors.initials: MH
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Winey
authors.forename: S
authors.initials: S
authors.lastname: Sazer
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000502:physiology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D064246:Mad2 Proteins; D008677:Metaphase / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D008941:Spindle Apparatus / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D014452:Ubiquitins / Q000235:genetics / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C100415:DSK2 protein, S cerevisiae; D005656:Fungal Proteins; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014452:Ubiquitins; C577696:mad2 protein, S pombe; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C093416:MPS1 protein, S cerevisiae