pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation
Cancer; Mechanisms of disease
| Autores: | , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2022 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:11351/8557 |
| Acesso em linha: | https://hdl.handle.net/11351/8557 http://hdl.handle.net/11351/8557 |
| Access Level: | Acceso aberto |
| Palavra-chave: | 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 |
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pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| title |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| spellingShingle |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation Boix Sanchez, Olga 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 |
| title_short |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| title_full |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| title_fullStr |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| title_full_unstemmed |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| title_sort |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| dc.creator.none.fl_str_mv |
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 |
| author |
Boix Sanchez, Olga |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
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 |
| dc.subject.none.fl_str_mv |
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 |
| topic |
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 |
| description |
Cancer; Mechanisms of disease |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11351/8557 http://hdl.handle.net/11351/8557 |
| url |
https://hdl.handle.net/11351/8557 http://hdl.handle.net/11351/8557 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Nature Communications;13 https://doi.org/10.1038/s41467-022-34529-6 |
| dc.rights.none.fl_str_mv |
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Portfolio |
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Nature Portfolio |
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Scientia reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869420023077928960 |
| spelling |
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activationBoix Sanchez, OlgaMartinez Pascale, MarionVidal, SantiagoGimenez Alejandre, MartaPalenzuela Diaz, LluísLorenzo-Sanz, LauraMoscoso, OlivierCiriaco Cortés, NikaolyNuciforo, Paolo GiovanniTian, Tian VVivancos Prellezo, AnaRamon y Cajal Agüeras, SantiagoAbad Mendez, MariaCàncer - Aspectes genèticsTranscriptomesDISEASES::NeoplasmsOther subheadings::Other subheadings::Other subheadings::/geneticsCHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::UbiquitinsPHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression::Transcription, Genetic::Genetic Phenomena::TranscriptomeENFERMEDADES::neoplasiasOtros calificadores::Otros calificadores::Otros calificadores::/genéticaCOMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::ubicuitinasFENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica::transcripción genética::fenómenos genéticos::transcriptomaCancer; Mechanisms of diseaseCàncer; Mecanismes de la malaltiaCáncer; Mecanismos de la enfermedadThe 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.Nature PortfolioInstitut 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, SpainVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/8557http://hdl.handle.net/11351/8557Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature Communications;13https://doi.org/10.1038/s41467-022-34529-6Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/85572026-05-29T05:05:01Z |
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