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PXD041225-1

PXD041225 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeted protein degradation using E2 ubiquitin-conjugating enzymes
DescriptionProteins can be targeted for degradation by using engineered molecular conjugates to enhance their interaction with eukaryotic ubiquitination machinery. For instance, the fusion of an E3 ubiquitin ligase to a suitable target binding domain creates a biological ‘Proteolysis-Targeting Chimera’ (bioPROTAC). Here we report an analogous approach where the target is recruited directly to an E2 ubiquitin-conjugating enzyme via an attached target binding domain. We demonstrate that E2 bioPROTACs can induce the degradation of the human proteins SHP2, KRAS and Human Antigen R (HuR). Taking advantage of both rational and unbiased combinatorial screening, we identified novel SHP2 degraders that possess unusually weak affinity. Finally, we explored the proteomic impact of E2 vs. E3 bioPROTACs to inform on their wider impact on the cellular proteome.
HostingRepositoryPRIDE
AnnounceDate2024-09-23
AnnouncementXMLSubmission_2024-09-23_04:33:44.471.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFiona Pachl
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-03-30 12:57:18ID requested
12024-09-23 04:33:45announced
22024-10-22 06:59:19announced2024-10-22: Updated project metadata.
Publication List
10.1038/s42003-024-06803-4;
Taylor JD, Barrett N, Martinez Cuesta S, Cassidy K, Pachl F, Dodgson J, Patel R, Eriksson TM, Riley A, Burrell M, Bauer C, Rees DG, Cimbro R, Zhang AX, Minter RR, Hunt J, Legg S, Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes. Commun Biol, 7(1):1179(2024) [pubmed]
Keyword List
submitter keyword: bioPROTAC
Contact List
Andrew Zhang
contact affiliationDiscovery Biology, AstraZeneca Pharmaceuticals
contact emailandrewzhang@astrazeneca.com
lab head
Fiona Pachl
contact affiliationAstraZeneca
contact emailfiona.pachl@astrazeneca.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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