PXD021255-1

PXD021255 is an original dataset announced via ProteomeXchange.

Title	Mapping the Degradable Kinome: A Resource for Expedited Degrader Development
Description	Targeted 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.
HostingRepository	PRIDE
AnnounceDate	2021-04-06
AnnouncementXML	Submission_2021-04-06_11:28:09.901.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-01 04:46:56	ID requested
⏵ 1	2021-04-06 11:28:10	announced

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]

submitter keyword: Ubiquitin, PROTAC, IMiD, Kinase, degrader, Ubiquitin proteasome system, targeted degradation, E3 ligase

Eric Fischer
contact affiliation	Department 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 email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/04/PXD021255

PRIDE project URI

• PRIDE
  1. PXD021255
     1. Label: PRIDE project
     2. Name: Mapping the Degradable Kinome: A Resource for Expedited Degrader Development