Cdc28/Cdk1 regulates spindle pole body duplication through phosphorylation of Spc42 and Mps1.
Duplication of the Saccharomyces cerevisiae spindle pole body (SPB) once per cell cycle is essential for bipolar spindle formation and accurate chromosome segregation during mitosis. We have investigated the role that the major yeast cyclin-dependent kinase Cdc28/Cdk1 plays in assembly of a core SPB component, Spc42, to better understand how SPB duplication is coordinated with cell cycle progression. Cdc28 is required for SPB duplication and Spc42 assembly, and we found that Cdc28 directly phosphorylates Spc42 to promote its assembly into the SPB. The Mps1 kinase, previously shown to regulate Spc42 phosphorylation and assembly, is also a Cdc28 substrate, and Cdc28 phosphorylation of Mps1 is needed to maintain wild-type levels of Mps1 in cells. Analysis of nonphosphorylatable mutants in SPC42 and MPS1 indicates that direct Spc42 phosphorylation and indirect regulation of Spc42 through Mps1 are two overlapping pathways by which Cdc28 regulates Spc42 assembly and SPB duplication during the cell cycle.
Department of Molecular, Cellular & Developmental Biology, University of Colorado, Boulder 80309 USA.
Sue L
SL
Jaspersen
Brenda J
BJ
Huneycutt
Thomas H
TH
Giddings
Katheryn A
KA
Resing
Natalie G
NG
Ahn
Mark
M
Winey
D000483:Alleles; D016203:CDC2 Protein Kinase / Q000502:physiology*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000502:physiology*; D002453:Cell Cycle; D018385:Centrosome / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D013058:Mass Spectrometry; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D012694:Serine / Q000737:chemistry; D008941:Spindle Apparatus; D013696:Temperature; D013912:Threonine / Q000737:chemistry
D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; D010750:Phosphoproteins; C432692:SPC42 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D013912:Threonine; D012694:Serine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; C093416:MPS1 protein, S cerevisiae