PXD001969

PXD001969 is an original dataset announced via ProteomeXchange.

Title	Mps1 Phosphorylation of the Molecular Chaperone Hsp90 Regulates Mitotic Checkpoint
Description	SUMMARY Mps1 protein kinase is required for accurate chromosome segregation during the mitotic checkpoint. The molecular chaperone Heat Shock Protein 90 (Hsp90) has been linked to Mps1 activity, however the molecular mechanismsunderlying this regulatory process remain elusive. We report that Mps1 directly phosphorylates a conserved threonine residue (T101 in yeast Hsp90 and T115 in human Hsp90) in the N domain of Hsp90. This phosphorylation regulates chaperone function by reducingHsp90 ATPase activity andfosteringits association with kinase client proteins including Mps1. Phosphorylation of T101is also essential for the mitotic checkpoint because it confers Mps1 stability and activity.Additionally,Mps1 phosphorylation of Hsp90 sensitizes cells to Hsp90 inhibitors and elevated Mps1 levels confer tumor selectivity on Hsp90 drugs.Finally,we identified Cdc14 as the phosphatasethat dephosphorylatesT101 and disruptsthe Mps1-Hsp90 interaction. This leads to degradation of Mps1,thusproviding a mechanism for its inactivation and mitotic exit.
HostingRepository	PRIDE
AnnounceDate	2016-01-27
AnnouncementXML	Submission_2016-01-27_08:21:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Donald Wolfgeher
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-24 09:43:46	ID requested
⏵ 1	2016-01-27 08:21:54	announced

Woodford MR, Truman AW, Dunn DM, Jensen SM, Cotran R, Bullard R, Abouelleil M, Beebe K, Wolfgeher D, Wierzbicki S, Post DE, Caza T, Tsutsumi S, Panaretou B, Kron SJ, Trepel JB, Landas S, Prodromou C, Shapiro O, Stetler-Stevenson WG, Bourboulia D, Neckers L, Bratslavsky G, Mollapour M, Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors. Cell Rep, 14(4):872-884(2016) [pubmed]

curator keyword: Biological

submitter keyword: Heat Shock Protein 90, Phosphorylation, Kinase, Phosphatase, Molecular Chaperones, Mitotic checkpoint, Mps1, Cdc14

Mehdi Mollapour PhD
contact affiliation	Department of Urology, Department of Biochemistry and Molecular Biology, Cancer Research Institute, SUNY Upstate Medical University, 750 E. Adams St., Syracuse, NY 13210, USA
contact email	mollapom@upstate.edu
lab head
Donald Wolfgeher
contact affiliation	University of Chicago
contact email	donw@uchicago.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001969
     1. Label: PRIDE project
     2. Name: Mps1 Phosphorylation of the Molecular Chaperone Hsp90 Regulates Mitotic Checkpoint