PXD016916-3

PXD016916 is an original dataset announced via ProteomeXchange.

Title	XPO1 amplification abrogates the effects of E571K XPO1 mutation in B-cell lymphoma
Description	XPO1 gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25% of primary mediastinal B-cell lymphomas (PMBL) and classical Hodgkin lymphomas (cHL) cases harboured a recurrent XPO1 point mutation (NM_003400, chr2:g61718472C>T) resulting in the E571K modification within the hydrophobic groove of the protein, the site of cargo proteins binding. We investigated the functional impact of XPO1E571K mutation using cell lines having various XPO1 status. We first confirmed that the mutation was present both within the XPO1 mRNA and the corresponding protein. In the U2940 cell line having a wild-type (wt) XPO1 gene, we introduced the E571K mutation using several CRISPR-Cas9 strategies. Using a barcoding method to trace the mutation, we observed that the mutation gave no advantage in vitro. Indeed, the effects of XPO1E571K mutation were hidden by the presence of the XPO1 wt allele. Strikingly, XPO1E571K mutation never occurred as homozygous or hemizygous in our patients��������� cohort. We further showed that XPO1E571K mutation modified selinexor binding to XPO1 and in turn, its sensitivity to this drug. We concluded that the balance between the wild-type and the mutated allele of XPO1 is a key element in defining XPO1 functions and oncogenic properties.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:13:03.716.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-02 02:44:48	ID requested
1	2020-09-30 23:21:02	announced
2	2020-10-19 00:10:49	announced	2020-10-19: Updated publication reference for PubMed record(s): 33007990.
⏵ 3	2024-10-22 05:13:07	announced	2024-10-22: Updated project metadata.

10.3390/cancers12102829;

Miloudi H, Bohers É, Guillonneau F, Taly A, Gibouin VC, Viailly PJ, Jego G, Grumolato L, Jardin F, Sola B, Mutation Modifies Exportin 1 Localisation and Interactome in B-cell Lymphoma. Cancers (Basel), 12(10):(2020) [pubmed]

submitter keyword: AP-MS, u2940, XPO1, Human cells,exportin 1, K1106 Primary mediastinal B-cell lymphomal lines, MedB1, Q-exactive plus

Brigitte Sola
contact affiliation	Normandie Univ, INSERM U1245, UNICAEN, Caen, France
contact email	brigitte.sola@unicaen.fr
lab head
François GUILLONNEAU
contact affiliation	ICO Angers
contact email	francois.guillonneau@parisdescartes.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/2020/10/PXD016916

PRIDE project URI

• PRIDE
  1. PXD016916
     1. Label: PRIDE project
     2. Name: XPO1 amplification abrogates the effects of E571K XPO1 mutation in B-cell lymphoma