N-terminal regions of Mps1 kinase determine functional bifurcation

Araki, Yasuhiro; Gombos, Linda; Migueleti, Suellen P.S.; Sivashanmugam, Lavanya; Antony, Claude; Schiebel, Elmar

doi:10.1083/jcb.200910027

Cited by 55 publications

(71 citation statements)

References 62 publications

(118 reference statements)

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“…Cdc31 orthologs, the centrins, do not contain an N-terminal CDK1 consensus site but are subject to phosphorylation in physiological and pathological situations such as cancer (Araki et al, 2010;Lutz et al, 2001;Yang et al, 2010). It will be of great interest to determine whether centrin phosphorylation by CDKs or alternative kinases can modulate the assembly of arrays of Sfi1 orthologs to control their functions in centrosomes in other eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

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Cell cycle control of spindle pole body duplication and splitting by Sfi1 and Cdc31 in fission yeast

Bouhlel

Ohta

Mayeux

et al. 2015

Journal of Cell Science

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Spindle pole biogenesis and segregation are tightly coordinated to produce a bipolar mitotic spindle. In yeasts, the spindle pole body (SPB) half-bridge composed of Sfi1 and Cdc31 duplicates to promote the biogenesis of a second SPB. Sfi1 accumulates at the half-bridge in two phases in Schizosaccharomyces pombe, from anaphase to early septation and throughout G2 phase. We found that the function of Sfi1-Cdc31 in SPB duplication is accomplished before septation ends and G2 accumulation starts. Thus, Sfi1 early accumulation at mitotic exit might correspond to half-bridge duplication. We further show that Cdc31 phosphorylation on serine 15 in a Cdk1 (encoded by cdc2) consensus site is required for the dissociation of a significant pool of Sfi1 from the bridge and timely segregation of SPBs at mitotic onset. This suggests that the Cdc31 N-terminus modulates the stability of Sfi1-Cdc31 arrays in fission yeast, and impacts on the timing of establishment of spindle bipolarity.

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Section: Discussionmentioning

confidence: 99%

“…Phosphorylation of Cdc31 by Mps1 was shown to be necessary for SPB duplication. Whether this phosphorylation is sufficient to promote half-bridge duplication remains unknown (Araki et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Cell cycle control of spindle pole body duplication and splitting by Sfi1 and Cdc31 in fission yeast

Bouhlel

Ohta

Mayeux

et al. 2015

Journal of Cell Science

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“…A collection of MPS1 alleles revealed that the kinase acts in multiple steps of the duplication pathway (7), and the kinase has been shown to phosphorylate numerous SPB components. These include Spc29 and Spc42, which are fungus specific, whose assembly and stability are controlled by Mps1 phosphorylation (14–16). The more widely conserved SPB components that are Mps1 substrates include centrin (Cdc31) (14), the γ-tubulin complex component Spc98 (17), and the Spc110 tether that holds the γ-tubulin complex (Tub4, Spc98, Spc97) to the SPB (18).…”

Section: Mps1 Functionsmentioning

confidence: 99%

The MPS1 Family of Protein Kinases

Liu

Winey

2012

Annu. Rev. Biochem.

191

220

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MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs.

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“…Mutation of the MELT motif compromises Bub1-Bub3 kinetochore localization and results in spindle checkpoint and cell growth defects [6][7][8]. Furthermore, diverse studies have suggested that defects in microtubule attachment promote Mps1 recruitment to the KMN (KNL1-Mis12-Ndc80) complex network [9][10][11].…”

Section: Introductionmentioning

confidence: 97%

Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint)

Thebault

Chirgadze

Dou

et al. 2012

Biochemical Journal

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The SAC (spindle assembly checkpoint) is a surveillance system that ensures the timely and accurate transmission of the genetic material to offspring. The process implies kinetochore targeting of the mitotic kinases Bub1 (budding uninhibited by benzamidine 1), BubR1 (Bub1 related) and Mps1 (monopolar spindle 1), which is mediated by the N-terminus of each kinase. In the present study we report the 1.8 Å (1 Å=0.1 nm) crystal structure of the TPR (tetratricopeptide repeat) domain in the N-terminal region of human Mps1. The structure reveals an overall high similarity to the TPR motif of the mitotic checkpoint kinases Bub1 and BubR1, and a number of unique features that include the absence of the binding site for the kinetochore structural component KNL1 (kinetochore-null 1; blinkin), and determinants of dimerization. Moreover, we show that a stretch of amino acids at the very N-terminus of Mps1 is required for dimer formation, and that interfering with dimerization results in mislocalization and misregulation of kinase activity. The results of the present study provide an important insight into the molecular details of the mitotic functions of Mps1 including features that dictate substrate selectivity and kinetochore docking.

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N-terminal regions of Mps1 kinase determine functional bifurcation

Abstract: Spindle pole body components Spc29 and Cdc31 are identified as targets of Mps1 kinase, which, when phosphorylated, regulate protein–protein interactions in the spindle pole body.

Cited by 55 publications

References 62 publications

Cell cycle control of spindle pole body duplication and splitting by Sfi1 and Cdc31 in fission yeast

Cell cycle control of spindle pole body duplication and splitting by Sfi1 and Cdc31 in fission yeast

The MPS1 Family of Protein Kinases

Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint)

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