PXD057186

PXD057186 is an original dataset announced via ProteomeXchange.

Title	SMAD nucleocytoplasmic shuttling relies on nucleoporin RanBP2 and VIM-AS1 long non-coding RNA during TGF-β signaling
Description	Activation of the transforming growth factor β (TGF-β) signaling leads to established hallmarks of cancer such as the epithelial-to-mesenchymal transition (EMT), initiating cancer dissemination and increasing chemoresistance. TGF-β signal by binding to its type I and II receptors, leading to parallel activation of SMAD proteins, ubiquitin ligases and protein kinases. Here, using a panel of tumor cells we show that TGF-β activation induces the expression of the mammalian nuclear long non-coding RNA (lncRNA) VIM-AS1 (Vimentin antisense RNA 1) variant 2 (v.2) via the formation of a complex among the transcriptional factors GATA6-SMAD-SPI1. Furthermore, transcriptomic analysis indicated VIM-AS1 enhancing TGF-β signaling and EMT, as further validated by functional gain or loss assays. Mechanistically, the TGF-β-induced VIM-AS1 v.2 enhanced SMAD nucleocytoplasmic shuttling by interacting with the N-terminus domain of the nucleoporin RanBP2 (Nup358), whereby acting as a scaffold molecule, facilitates the binding of RanBP2 with SMAD2/3 and its further nuclear import. Finally, VIM-AS1 increases invasion and motility of tumor cells and emerges as a promising therapeutic target to sensitize cancer cells to chemotherapeutic drugs. Hence, we delineated a novel signaling mechanism for VIM-AS1 v.2 facilitating TGF-β response in tumor cells via SMAD nucleocytoplasmic shuttling.
HostingRepository	PRIDE
AnnounceDate	2026-01-26
AnnouncementXML	Submission_2026-01-25_16:08:27.176.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liisa Arike
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-25 01:56:36	ID requested
⏵ 1	2026-01-25 16:08:28	announced

10.1093/nar/gkaf1526;

Rodrigues-Junior DM, Ali MM, Itoh Y, Ferreira MS, Heldin J, Fu H, Hoelz A, Heldin CH, Moustakas A, signaling. Nucleic Acids Res, 54(2):(2026) [pubmed]

submitter keyword: Cancer

epithelial-to-mesenchymal transition

Long non-coding RNA

Nucleoporin

SMAD

Transforming Growth Factor β

VIM-AS1

Aristidis Moustakas
contact affiliation	Professor at Department of Medical Biochemistry and Microbiology; Biochemistry and Cancer;Uppsala University, Sweden
contact email	aris.moustakas@imbim.uu.se
lab head
Liisa Arike
contact affiliation	PhD
contact email	liisaarike@gmail.com
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/2026/01/PXD057186

PRIDE project URI

• PRIDE
  1. PXD057186
     1. Label: PRIDE project
     2. Name: SMAD nucleocytoplasmic shuttling relies on nucleoporin RanBP2 and VIM-AS1 long non-coding RNA during TGF-β signaling