PXD014837 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Uncoupling of PARP1 Trapping and Inhibition Using Selective PARP1 Degradation |
Description | PARP1 inhibitors (PARPi) are known to kill tumor cells via two mechanisms (i.e., PARP1 catalytic inhibition vs. PARP1 trapping). The relative contribution of these two pathways in mediating the cytotoxicity of PARPi, however, is incompletely understood. Here we designed a series of small molecule PARP degraders. Treatment with one such compound iRucaparib (1) results in highly efficient and specific PARP1 degradation. iRucaparib blocks the enzymatic activity of PARP1 in vitro, and PARP1-mediated PARylation signaling in intact cells. This strategy mimics PARP1 genetic depletion, which enables the pharmacological decoupling of PARP1 inhibition from PARP1 trapping. Finally, by depleting PARP1, iRucaparib protects muscle cells and primary cardiomyocytes from DNA damage-induced energy crisis and cell death. In summary, these compounds represent “non-trapping” PARP1 degraders that block both the catalytic activity and scaffolding effects of PARP1, providing an ideal approach for the amelioration of the various pathological conditions caused by PARP1 hyperactivation. |
HostingRepository | PRIDE |
AnnounceDate | 2019-08-01 |
AnnouncementXML | Submission_2019-08-01_01:24:26.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Shuai Wang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-07-31 01:21:54 | ID requested | |
⏵ 1 | 2019-08-01 01:44:25 | announced | |
2 | 2019-11-08 00:44:53 | announced | 2019-11-08: Updated publication reference for PubMed record(s): 31659317. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: iRucaparib-TP3, vRucaparib-TP4, PARP1 degradation, BT-549 cell |
Contact List
Yonghao Yu |
contact affiliation | Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA. |
contact email | Yonghao.Yu@UTSouthwestern.edu |
lab head | |
Shuai Wang |
contact affiliation | UT Southwestern Medical Center |
contact email | shuai.wang@UTSouthwestern.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD014837
- Label: PRIDE project
- Name: Uncoupling of PARP1 Trapping and Inhibition Using Selective PARP1 Degradation