PXD026181-1

PXD026181 is an original dataset announced via ProteomeXchange.

Title	TINCR lncRNA encodes a ubiquitin-like protein that activates CDC42, promotes epithelial differentiation and suppresses tumor growth
Description	The human transcriptome contains thousands of small open reading frames (sORFs) that have been largely overlooked because of their small size. Some of these sORFs code for bioactive small proteins, although none of them have been associated with the regulation of cell identity. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) with a SUMO interacting motif (SIM) that is expressed in many epithelia. We find that pTINCR binds to SUMO and modifies global cell SUMOylation. One of its main binding partners is CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and for epidermal differentiation. We show that pTINCR increases CDC42 SUMOylation and promotes its activation in a SIM-dependent manner. Indeed, by gain- and loss-of-function studies we demonstrate that pTINCR is a key regulator of epithelial cell differentiation in vitro and promotes epidermal differentiation in vivo. Consistent with its pro-differentiation role, pTINCR expression is lost in human cutaneous squamous cell carcinomas (cSCC), and its overexpression reduces malignancy in cSCC patient-derived xenografts (PDXs). Of note, we show that the tumor suppressor p53 upregulates TINCR and increases pTINCR protein levels. Moreover, the expression of TINCR in epithelial cancers correlates with better prognosis. Our results identify pTINCR as a novel regulator of epithelial differentiation with tumor suppressor activity. More generally, our findings suggest that the proteome encoded by previously assumed non-coding RNAs can indeed be a source of new regulators of cell identity relevant for cancer.
HostingRepository	PRIDE
AnnounceDate	2022-10-06
AnnouncementXML	Submission_2022-10-06_00:22:13.238.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Olga Boix
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-20 22:39:11	ID requested
⏵ 1	2022-10-06 00:22:13	announced

Dataset with its publication pending

submitter keyword: sORFs

non-canonical ORFs

microproteins

micropeptides

lncRNAs

UBLs

SUMO

CDC42

cell identity

cellular plasticity

cell differentiation

epidermis

cancer

squamous carcinoma

María Abad Méndez
contact affiliation	Vall d'Hebron Institute of Oncology
contact email	mabad@vhio.net
lab head
Olga Boix
contact affiliation	VHIO
contact email	oboix@vhio.net
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026181
     1. Label: PRIDE project
     2. Name: TINCR lncRNA encodes a ubiquitin-like protein that activates CDC42, promotes epithelial differentiation and suppresses tumor growth