Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling Journal Article

   

Authors:	Maciejowski, J.; George, K. A.; Terret, M. E.; Zhang, C.; Shokat, K. M.; Jallepalli, P. V.
Article Title:	Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling
Abstract:	The spindle assembly checkpoint (SAC) in mammals uses cytosolic and kinetochore-based signaling pathways to inhibit anaphase. In this study, we use chemical genetics to show that the protein kinase Mps1 regulates both aspects of the SAC. Human MPS1-null cells were generated via gene targeting and reconstituted with either the wild-type kinase (Mps1wt) or a mutant version (Mps1as) sensitized to bulky purine analogues. Mps1 inhibition sharply accelerated anaphase onset, such that cells completed mitosis in 12 min, and prevented Cdc20's association with either Mad2 or BubR1 during interphase, i.e., before the appearance of functional kinetochores. Furthermore, intramitotic Mps1 inhibition evicted Bub1 and all other known SAC transducers from the outer kinetochore, but contrary to a recent study, did not perturb aurora B-dependent phosphorylation. We conclude that Mps1 has two complementary roles in SAC regulation: (1) initial cytoplasmic activation of Cdc20 inhibitors and (2) recruitment of factors that promote sustained anaphase inhibition and chromosome biorientation to unattached kinetochores. © 2010 Maciejowski et al.
Keywords:	signal transduction; unclassified drug; protein function; mammalia; cell cycle proteins; cell division; complex formation; protein targeting; wild type; regulatory mechanism; protein-serine-threonine kinases; cell line, transformed; anaphase; chemical genetics; mitosis spindle; inhibition kinetics; cell cycle m phase; multiprotein complexes; calcium-binding proteins; checkpoint kinase 1; cell cycle regulation; chromosomes, human; repressor proteins; protein kinase; cytosol; centromere; bub1 related protein; cell cycle protein 20; protein mad2; protein mps1; interphase; null cell; kinetochores
Journal Title:	Journal of Cell Biology
Volume:	190
Issue:	1
ISSN:	0021-9525
Publisher:	Rockefeller University Press
Date Published:	2010-07-12
Start Page:	89
End Page:	100
Language:	English
DOI:	10.1083/jcb.201001050
PUBMED:	20624902
PROVIDER:	scopus
PMCID:	PMC2911671
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77954706607&partnerID=40&md5=7f0bd9edd18259d90917b36c3930410a
Notes:	--- - "Cited By (since 1996): 8" - "Export Date: 20 April 2011" - "CODEN: JCLBA" - "Source: Scopus"

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