PXD014786

PXD014786 is an original dataset announced via ProteomeXchange.

Title	A proteomic approach for characterizing trastuzumab-emtansine modified for nuclear directed localization that enhances cytotoxicity identifies regulatory nuclear transport receptor.
Description	We used the approved antibody-drug conjugate trastuzumab-emtansine and the HER2+ cell line SKBR3. We also used a novel technology termed cell accumulator (Accum) that enables mAbs to escape endosome entrapment and localize to the cell nucleus without abrogating antibody affinity or specificity to target antigens. Accum harbors a well-known nuclear localization signal (NLS) sequence recognized by the classic nuclear transportation receptor (NTR) complex alpha-importin/importin-beta. Accum-modification of T-DM1 resulted in a significant increase in cytotoxic potency. We sought to understand the mechanisms through which Accum-T-DM1 localized to the nucleus and increased tumor cell killing effectiveness.
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_11:16:09.920.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vincent Lacasse
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-29 01:36:27	ID requested
⏵ 1	2021-09-08 11:16:11	announced

Lacasse V, Beaudoin S, Jean S, Leyton JV, A Novel Proteomic Method Reveals NLS Tagging of T-DM1 Contravenes Classical Nuclear Transport in a Model of HER2-Positive Breast Cancer. Mol Ther Methods Clin Dev, 19():99-119(2020) [pubmed]

submitter keyword: Affinity purification, protein-protein interaction, nuclear transport, SK-BR-3, Antibody-drug conjugate, nano-LC-MS/MS

Jeffrey Victor Leyton
contact affiliation	Department of Nuclear Medicine and Radiobiology Faculty of Medicine and Health Sciences Université de Sherbrooke Sherbrooke, Quebec, Canada
contact email	jeffrey.leyton@usherbrooke.ca
lab head
Vincent Lacasse
contact affiliation	Université de Sherbrooke
contact email	vincent.lacasse@usherbrooke.ca
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/2021/09/PXD014786

PRIDE project URI

• PRIDE
  1. PXD014786
     1. Label: PRIDE project
     2. Name: A proteomic approach for characterizing trastuzumab-emtansine modified for nuclear directed localization that enhances cytotoxicity identifies regulatory nuclear transport receptor.