2026-04-17T17:00:09Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/85572024-12-13T10:55:24Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation Boix Sanchez, Olga Martinez Pascale, Marion Vidal, Santiago Gimenez Alejandre, Marta Palenzuela Diaz, Lluís Lorenzo-Sanz, Laura Moscoso, Olivier Ciriaco Cortés, Nikaoly Nuciforo, Paolo Giovanni Tian, Tian V Vivancos Prellezo, Ana Ramon y Cajal Agüeras, Santiago Abad Mendez, Maria Institut Català de la Salut [Boix O, Martinez M, Giménez-Alejandre M, Palenzuela L, Abad M] Cellular Plasticity and Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Vidal S] Centro de Investigación en Medicina Molecular (CIMUS), Universidad de Santiago de Compostela and Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain. [Lorenzo-Sanz L] Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Moscoso O, Ciriaco N, Ramón Y Cajal S] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Patologia Molecular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona and Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Barcelona, Spain. [Nuciforo P] Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Tian TV] Noncolorectal Gastrointestinal Cancer Translational Research Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Vivancos A] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Càncer - Aspectes genètics Transcriptomes DISEASES::Neoplasms Other subheadings::Other subheadings::Other subheadings::/genetics CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Ubiquitins PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression::Transcription, Genetic::Genetic Phenomena::Transcriptome ENFERMEDADES::neoplasias Otros calificadores::Otros calificadores::Otros calificadores::/genética COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::ubicuitinas FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica::transcripción genética::fenómenos genéticos::transcriptoma Cancer; Mechanisms of disease Càncer; Mecanismes de la malaltia Cáncer; Mecanismos de la enfermedad 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. Work in the Abad lab is supported by VHIO, Fero Foundation, La Caixa Foundation, Asociación Española Contra el Cancer (AECC), La Mutua Foundation and by grants from the Spanish Ministry of Science and Innovation (SAF2015-69413-R; RTI2018-102046-B-I00). M.A. was recipient of a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation (RYC-2013-14747). O.B. is recipient of a FPI-AGAUR fellowship from Generalitat de Catalunya. We also acknowledge funding from grant PGC2018-094091-B-I00 from the Spanish Government. 2022-11-30T08:32:56Z 2022-11-30T08:32:56Z 2022-11-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Boix O, Martinez M, Vidal S, Giménez-Alejandre M, Palenzuela L, Lorenzo-Sanz L, et al. pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation. Nat Commun. 2022 Nov 11;13:6840. 2041-1723 https://hdl.handle.net/11351/8557 10.1038/s41467-022-34529-6 36369429 http://hdl.handle.net/11351/8557 eng Nature Communications;13 https://doi.org/10.1038/s41467-022-34529-6 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Nature Portfolio Scientia