High impact information on MPS1

• The mouse Mps1p-like kinase regulates centrosome duplication [1].
• Spindle assembly checkpoint mutants overexpressing Mps1p pass through mitosis without delay and can produce viable progeny, which demonstrates that the arrest of wild-type cells results from inappropriate activation of the checkpoint in cells whose spindle is fully functional [2].
• Ipl1p is required to maintain the spindle checkpoint that is induced by overexpression of the protein kinase Mps1 [3].
• The Skp1's interaction with Bub1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization, kinetochore assembly defects, or Mps1 overexpression [4].
• We conclude that Mps1p regulates assembly of the integral SPB component Spc42p during SPB duplication [5].

Biological context of MPS1

• Unlike cells delayed in mitosis by spindle damage or MPS1 kinase overexpression, hyperphosphorylated forms of the Mad1p checkpoint protein did not accumulate [6].
• The mechanism for the increase in ploidy may occur through MPS1 function [7].
• This phenotype may arise in part from reduced Mps1p function: although Mps1p protein levels are unaffected by the cdc37-1 mutation, kinase activity is markedly reduced [8].
• Here we show that the Saccharomyces cerevisiae MPS1 gene product, an essential protein kinase required for spindle pole body (SPB) duplication (Winey et al., 1991; Lauze et al., 1995), is also required for M-phase check-point function [9].
• The MPS1 gene has been previously identified by a mutant allele that shows defects in spindle pole body (SPB) duplication and cell cycle control [10].

Anatomical context of MPS1

• Arrest of mitosis upon microtubule depolymerization by nocodazole is also conditionally absent in mps1 strains [9].
• Budding yeast Mps1p kinase has been implicated in both the duplication of microtubule-organizing centers and the spindle assembly checkpoint [11].

Associations of MPS1 with chemical compounds

• Phosphoamino acid analysis of substrates phosphorylated by Mps1p indicates that this kinase can phosphorylate serine, threonine and tyrosine residues, identifying Mps1p as a dual specificity protein kinase [10].
• In contrast, hydroxyurea arrest and a number of other cdc mutant arrest phenotypes are unaffected by mps1 alleles [9].
• Ser(60), Thr(64), and Thr(68) are the major sites in Spc110p phosphorylated by Mps1p in vitro, and alanine substitution at these sites abolishes the mitosis-specific isoform in vivo [12].

Physical interactions of MPS1

• The yeast CDC37 gene interacts with MPS1 and is required for proper execution of spindle pole body duplication [8].
• Yeast Dam1p is required to maintain spindle integrity during mitosis and interacts with the Mps1p kinase [13].

Regulatory relationships of MPS1

• Our data now point to the protein kinase Mps1p triggering a new parallel branch of the spindle checkpoint in which Bub2p blocks Dbf2p function [14].

Other interactions of MPS1

• MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication [15].
• Suppression is allele specific, and synthetic lethal interactions occur between mps1 and cdc37 alleles [8].
• Distinct temporal requirements for the CDC31, MPS1, and MPS2 gene functions during the SPB duplication cycle further demonstrate the individual roles of these genes in the morphogenetic pathway [15].
• This suggests that the Bub1p and Mps1p kinases act together at an early step in generating the spindle damage signal [6].
• Mob1p is a phosphoprotein in vivo and a substrate for the Mps1p kinase in vitro [7].

Analytical, diagnostic and therapeutic context of MPS1

• The MPS1 gene is found by electron microscopy to be essential for proper formation of the site at which the new SPB normally arises adjacent to the existing one [15].
• An epitope-tagged version of Mps1p (Mps1p-myc) localizes to SPBs and kinetochores by immunofluorescence microscopy and immuno-EM analysis [5].

References