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Abstract: The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.
Fuente: Nature Communications (2022) 13: 6840
Publisher: Nature Publishing Group
Publication date: 11/11/2022
No. of pages: 22
Publication type: Article
DOI: 10.1038/s41467-022-34529-6
ISSN: 2041-1723
Spanish project: SAF2015-69413-R
Publication Url: https://doi.org/10.1038/s41467-022-34529-6
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BOIX, OLGA
MARTÍNEZ, MARION
VIDAL, SANTIAGO
GIMÉNEZ-ALEJANDRE, MARTA
PALENZUELA, LLUÍS
LORENZO-SANZ, LAURA
LAURA QUEVEDO PALACIO
MOSCOSO, OLIVIER
RUIZ-ORERA, JORGE
XIMÉNEZ-EMBÚN, PILAR
CIRIACO, NIKAOLY
NUCIFORO, PAOLO
ATTOLILNI, CAMILLE STEPHAN-OTTO
ALBÀ, M. MAR
MUÑOZ, JAVIER
VIAN, TIAN V.
IGNACIO VARELA EGOCHEAGA
VIVANCOS, ANA
RAMÓN Y CAJAL, SANTIAGO
MUÑOZ, PURIFICACIÓN
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