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PXD021255-1

PXD021255 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMapping the Degradable Kinome: A Resource for Expedited Degrader Development
DescriptionTargeted protein degradation refers to the use of small molecule inducers of ubiquitin-dependent degradation of proteins and enables the development of drugs to previously inaccessible targets. Degrader development is an empirical process due to a poor understanding of the key properties that require optimization. Here we established a synthetic chemistry and chemo-proteomics platform to annotate the ‘degradable kinome’. This first comprehensive dataset provides chemical leads for approximately 200 distinct kinase targets and demonstrates that the current practice of starting degrader design from the highest potency binder is often inadequate to generate an optimal degrader. This rich chemo-proteomic dataset supports the development of selective and multi-kinase degraders and also provides unique chemical tools to answer fundamental questions regarding ubiquitin-mediated kinase degradation, such as the requirement for p97 unfoldase activity for degradation by the proteasome. This work provides a blueprint for evaluating targeted degradation across entire gene families, which will serve to accelerate degrader development beyond the kinome.
HostingRepositoryPRIDE
AnnounceDate2021-04-06
AnnouncementXMLSubmission_2021-04-06_11:28:09.901.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEric Fischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-01 04:46:56ID requested
12021-04-06 11:28:10announced
Publication List
Donovan KA, Ferguson FM, Bushman JW, Eleuteri NA, Bhunia D, Ryu S, Tan L, Shi K, Yue H, Liu X, Dobrovolsky D, Jiang B, Wang J, Hao M, You I, Teng M, Liang Y, Hatcher J, Li Z, Manz TD, Groendyke B, Hu W, Nam Y, Sengupta S, Cho H, Shin I, Agius MP, Ghobrial IM, Ma MW, Che J, Buhrlage SJ, Sim T, Gray NS, Fischer ES, Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development. Cell, 183(6):1714-1731.e10(2020) [pubmed]
Keyword List
submitter keyword: Ubiquitin, PROTAC, IMiD, Kinase, degrader, Ubiquitin proteasome system, targeted degradation, E3 ligase
Contact List
Eric Fischer
contact affiliationDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact emaileric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliationDana-Farber Cancer Institute
contact emaileric_fischer@dfci.harvard.edu
dataset submitter
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Dataset FTP location
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