PXD042696

PXD042696 is an original dataset announced via ProteomeXchange.

Title	Proteomic profile of BxPC3 cells after RAD51 inhibition by treatment with BRC4
Description	RAD51 protein is an evolutionarily conserved recombinase that plays a central role in homologous recombination (HR) and DNA double strand break (DSB) repair. RAD51 inactivation by small molecules has been proposed as a strategy to impair the BRCA2/RAD51 binding and, ultimately, the HR pathway, with the aim to make cancer cells more sensitive to PARP inhibitors (PARPi). This strategy, which mimics a synthetic lethality (SL) approach, has been successfully assayed in vitro by using myr-BRC4, a peptide derived from the fourth BRC repeat of BRCA2, being the strongest reported natural RAD51 binder. The present study applies a method to obtain a proteomic fingerprint for RAD51 inhibition by the myr-BRC4 peptide (designed for a more efficient cell entry) using a mass spectroscopy (MS) proteomic approach. We performed a comparative proteomic profiling of the myr-BRC4 treated vs. untreated BxPC-3 pancreatic cancer cells and evaluated the differential expression of proteins. Among the identified proteomic hits, we focused our attention on proteins shared by both the RAD51 and the BRCA2 interactomes, and on those whose reduction showed high statistical significance. Three downregulated proteins were identified (FANCI, FANCD2, and RPA3) and protein downregulation was confirmed through immunoblotting analysis, validating the MS approach. Our results suggest that, being a direct consequence of RAD51 inhibition, the detection of FANCD2, FANCI, and RPA3 downregulation could be used as an indicator for monitoring HR impairment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:42.715.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-02 12:43:03	ID requested
1	2023-08-15 09:14:48	announced
⏵ 2	2023-11-14 09:04:50	announced	2023-11-14: Updated project metadata.

Previtali V, Myers SH, Poppi L, Wynne K, Casamassima I, Girotto S, Di Stefano G, Farabegoli F, Roberti M, Oliviero G, Cavalli A, Preomic profile of BxPC-3 cells after treatment with BRC4. J Proteomics, 288():104983(2023) [pubmed]

submitter keyword: Proteomie, RAD51, BxPC3 cells, BRC4.

Giorgio Oliviero
contact affiliation	Systems Biology Ireland, University College Dublin.
contact email	giorgio.oliviero.giorgio@gmail.com
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042696
     1. Label: PRIDE project
     2. Name: Proteomic profile of BxPC3 cells after RAD51 inhibition by treatment with BRC4