PXD023252

PXD023252 is an original dataset announced via ProteomeXchange.

Title	DDX5 promotes prostate cancer progression and activates DNA repair pathway
Description	The small heat shock protein Hsp27 has been long demonstrated as a major driver of Castration Resistant Prostate Cancer (CRPC) progression via an androgen receptor-independent pathway. In the light of identification of its molecular mechanisms, we found that the RNA helicase protein DDX5 was an interactor of Hsp27 and DDX5 expression was regulated by Hsp27 through its cytoprotective function. We showed that DDX5 was overexpressed in a large collection of human samples in aggressive PCs, especially CRPC. Here, we described the protein-protein interaction network of DDX5 which were identified in four human prostate cell lines (PNT1A, LNCaP, DU-145 and PC-3) representing different disease stages using immunoaffinity purification and quantitative mass spectrometry. The DDX5 interactome in CRPC cells was enriched in several functions (DNA damage response, translation, transcription, RNA stability, and DNA conformation changes) involved in disease progression. Furthermore, we found a new critical function of DDX5 in DNA damage repair in CRPC and validated the interaction of DDX5 with the DNA repair complex Ku70/Ku86 which plays a pivotal role in the NHEJ process. We also showed that DDX5 overexpression conferred resistance to DNA damage poisoners (such as irradiation and cisplatin) in CRPC, a feature that could lead to genome maintenance, tumor progression and treatment resistance.
HostingRepository	PRIDE
AnnounceDate	2022-08-21
AnnouncementXML	Submission_2022-08-21_14:35:03.910.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AUDEBERT Stephane
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-21 02:47:55	ID requested
⏵ 1	2022-08-21 14:35:04	announced

Le TK, Cherif C, Omabe K, Paris C, Lannes F, Audebert S, Baudelet E, Hamimed M, Barbolosi D, Finetti P, Bastide C, Fazli L, Gleave M, Bertucci F, Ta, ï, eb D, Rocchi P, DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer. Mol Ther, 31(2):471-486(2023) [pubmed]

submitter keyword: DDX5, interactome, HSP27, Castration Resistant Prostate Cancer (CRPC), DNA damage response, LC-MSMS, AP-MS

ROCCHI Palma
contact affiliation	Centre de Recherche en Cancérologie de Marseille, CRCM Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact email	palma.rocchi@inserm.fr
lab head
AUDEBERT Stephane
contact affiliation	Pharmacology department
contact email	stephane.audebert@inserm.fr
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/2022/08/PXD023252

PRIDE project URI

• PRIDE
  1. PXD023252
     1. Label: PRIDE project
     2. Name: DDX5 promotes prostate cancer progression and activates DNA repair pathway