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 Detalle_Publicacion

pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation

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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Nature Communications (2022) 13: 6840

Editorial: Nature Publishing Group

 Fecha de publicación: 11/11/2022

Nº de páginas: 22

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41467-022-34529-6

ISSN: 2041-1723

 Proyecto español: SAF2015-69413-R

Url de la publicación: https://doi.org/10.1038/s41467-022-34529-6

Autoría

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.

VIVANCOS, ANA

RAMÓN Y CAJAL, SANTIAGO

MUÑOZ, PURIFICACIÓN