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PXD012692

PXD012692 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDiscovery of covalent CDK14 inhibitors with pan-TAIRE family specificity
DescriptionCyclin dependent kinase 14 (CDK14) and other TAIRE family kinases (CDKs 15-18) are proteins that lack functional annotation but are frequent off-targets of clinical kinase inhibitors. In this study we develop and characterize FMF-04-159-2, the first tool compound that specifically targets CDK14 covalently and possesses a TAIRE kinase-biased selectivity profile. This tool compound and its reversible analog were used to characterize the cellular consequences of covalent CDK14 inhibition, including an unbiased investigation using phospho-proteomics. To reduce confounding off-target activity, washout conditions were used to deconvolute CDK14-specific effects. This investigation suggested that CDK14 plays a supporting role in cell cycle regulation, particularly mitotic progression, and identified putative CDK14 substrates using proteomics and phospho-proteomics experiments to characterize compound effects. Together these results represent an important step forward in understanding the cellular consequences of inhibiting CDK14 kinase activity.
HostingRepositoryPRIDE
AnnounceDate2019-03-29
AnnouncementXMLSubmission_2019-04-03_01:59:28.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMatthew Berberich
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-02-13 06:40:32ID requested
12019-03-29 07:48:14announced
22019-04-03 01:59:29announcedUpdated publication reference for PubMed record(s): 30930164.
Publication List
Ferguson FM, Doctor ZM, Ficarro SB, Browne CM, Marto JA, Johnson JL, Yaron TM, Cantley LC, Kim ND, Sim T, Berberich MJ, Kalocsay M, Sorger PK, Gray NS, Discovery of Covalent CDK14 Inhibitors with Pan-TAIRE Family Specificity. Cell Chem Biol, 26(6):804-817.e12(2019) [pubmed]
Keyword List
submitter keyword: CDK14, TAIRE kinase, covalent inhibitor, cell-cycle, mitosis, druggable genome
Contact List
Nathanael S. Gray
contact affiliationDana Farber Cancer Institute, Cancer Biology / Harvard Medical School, Biological Chemistry and Molecular Pharmacology
contact emailnathanael_gray@dfci.harvard.edu
lab head
Matthew Berberich
contact affiliationHarvard Program In Therapeutic Science/Harvard Medical School
contact emailmatthew_berberich@hms.harvard.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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