PXD034248 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The E3 ubiquitin ligase adaptor cereblon targets the C-terminal cyclic imide degron |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-07-28 |
AnnouncementXML | Submission_2022-07-28_04:02:37.482.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Christina Woo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | dehydrated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos; LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-06-01 05:12:49 | ID requested | |
⏵ 1 | 2022-07-28 04:02:37 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Cereblon, degron, cyclic imide, PROTAC |
Contact List
Christina Woo |
contact affiliation | Department of Chemistry and Chemical Biology, Harvard University |
contact email | cwoo@chemistry.harvard.edu |
lab head | |
Christina Woo |
contact affiliation | Harvard University |
contact email | cwoo@chemistry.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034248
- Label: PRIDE project
- Name: The E3 ubiquitin ligase adaptor cereblon targets the C-terminal cyclic imide degron