PXD012673

PXD012673 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-12 05:18:17	ID requested
⏵ 1	2019-11-12 18:32:26	announced

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]

curator keyword: Biological

submitter keyword: apoptosis, CBP, DBC1, p53, ubiquitin, LC-MSMS

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD012673

PRIDE project URI

• PRIDE
  1. PXD012673
     1. Label: PRIDE project
     2. Name: DBC1 regulates p53 stability via inhibition of CBP-dependent p53 polyubiquitination