PXD012673 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | DBC1 regulates p53 stability via inhibition of CBP-dependent p53 polyubiquitination |
Description | The control of p53 protein stability is critical to its tumor suppressor functions. The CREB Binding Protein (CBP) transcriptional coactivator co-operates with MDM2 to maintain normally low physiologic p53 levels in cells via an exclusively cytoplasmic ‘E4’ polyubiquitination activity. Utilizing mass spectrometry to identify nuclear and cytoplasmic CBP interacting proteins that regulate compartmentalized CBP E4 activity, we identified Deleted in Breast Cancer 1 (DBC1) as a stoichiometric CBP-interacting protein that negatively regulates CBP–dependent p53 polyubiquitination, stabilizes p53, and augments p53-dependent apoptosis. TCGA analysis demonstrated that solid tumors often retain wild type p53 alleles in conjunction with DBC1 loss, supporting the hypothesis that DBC1 is selected for disruption during carcinogenesis as a surrogate for p53 functional loss. As DBC1 maintains p53 stability in the nucleus where p53 exerts its tumor suppressive transcriptional function, replacement of DBC1 functionality in DBC1-deleted tumors might also enhance p53 function and chemosensitivity for therapeutic benefit. |
HostingRepository | PRIDE |
AnnounceDate | 2019-11-13 |
AnnouncementXML | Submission_2019-11-12_18:32:24.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | JJ Park |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | S-carboxamidoethyl-L-cysteine; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-02-12 05:18:17 | ID requested | |
⏵ 1 | 2019-11-12 18:32:26 | announced | |
Publication List
Akande OE, Damle PK, Pop M, Sherman NE, Szomju BB, Litovchick LV, Grossman SR, DBC1 Regulates p53 Stability via Inhibition of CBP-Dependent p53 Polyubiquitination. Cell Rep, 26(12):3323-3335.e4(2019) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: apoptosis, CBP, DBC1, p53, ubiquitin, LC-MSMS |
Contact List
Steven R. Grossman |
contact affiliation | Department of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA, USA |
contact email | steven.grossman@vcuhealth.org |
lab head | |
JJ Park |
contact affiliation | University of Virginia |
contact email | jp2ht@virginia.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD012673
- Label: PRIDE project
- Name: DBC1 regulates p53 stability via inhibition of CBP-dependent p53 polyubiquitination