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PXD034248

PXD034248 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe E3 ubiquitin ligase adaptor cereblon targets the C-terminal cyclic imide degron
DescriptionThe E3 ligase factor cereblon (CRBN) is a target of thalidomide and lenalidomide, which are therapeutic agents used in the treatment of hematopoietic malignancies and as ligands for targeted protein degradation. These agents are proposed to mimic a naturally occurring degron; however, the structural motif recognized by the thalidomide-binding domain of CRBN is unknown. Here, we report that C-terminal cyclic imides, post-translational modifications that arise from intramolecular cyclization of glutamine or asparagine residues, are degrons for CRBN. Dipeptides bearing the cyclic imide degron are substitutes for thalidomide when embedded within bifunctional small molecule degraders. Installation of the degron to the C-terminus of proteins induces CRBN-dependent ubiquitylation and degradation in vitro and in cells. C-Terminal cyclic imides are previously underappreciated post-translational modifications found throughout the human proteome that are endogenously recognized and removed by CRBN. The discovery of the cyclic imide degron defines a novel regulatory process controlled by these modifications, which may impact the development of therapeutic agents that engage CRBN.
HostingRepositoryPRIDE
AnnounceDate2022-07-28
AnnouncementXMLSubmission_2022-07-28_04:02:37.482.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristina Woo
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListdehydrated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos; LTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-06-01 05:12:49ID requested
12022-07-28 04:02:37announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Cereblon, degron, cyclic imide, PROTAC
Contact List
Christina Woo
contact affiliationDepartment of Chemistry and Chemical Biology, Harvard University
contact emailcwoo@chemistry.harvard.edu
lab head
Christina Woo
contact affiliationHarvard University
contact emailcwoo@chemistry.harvard.edu
dataset submitter
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