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| Home > Articles > Published articles > pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
(Vall d'Hebron Institut d'Oncologia) (Institut d'Investigació Biomèdica de Bellvitge) (Universidad de Cantabria) (Max Delbrück Center for Molecular Medicine in the Helmholtz Association) (Centro Nacional de Investigaciones Oncológicas) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Vall d'Hebron Institut d'Oncologia) (Institute for Research in Biomedicine (IRB Barcelona)) (Centro Nacional de Investigaciones Oncológicas) (Vall d'Hebron Institut d'Oncologia) (Universidad de Cantabria) (Vall d'Hebron Institut d'Oncologia) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Centro Nacional de Biotecnología (Madrid)) (Vall d'Hebron Institut d'Oncologia)| Date: | 2022 |
| 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. Small proteins encoded by previously assumed non-coding RNAs can have cell regulatory functions. Here the authors report that TINCR lncRNA encodes pTINCR, a ubiquitin-like protein (UBL) that promotes epithelial differentiation through the SUMOylation and activation of CDC42, and it has tumour suppressor activity in epithelial cancers. |
| Grants: | Ministerio de Economía, Industria y Competitividad SAF2015-69413-R Agencia Estatal de Investigación RTI2018-102046-B-I00 Ministerio de Economía, Industria y Competitividad RYC-2013-14747 Agencia Estatal de Investigación PGC2018-094091-B-I00 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Mechanisms of disease ; Cancer |
| Published in: | Nature communications, Vol. 13 (november 2022) , ISSN 2041-1723 |
