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| Item Type: | Article |
|---|---|
| Title: | pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation |
| Creators Name: | Boix, O. and Martinez, M. and Vidal, S. and Giménez-Alejandre, M. and Palenzuela, L. and Lorenzo-Sanz, L. and Quevedo, L. and Moscoso, O. and Ruiz-Orera, J. and Ximénez-Embún, P. and Ciriaco, N. and Nuciforo, P. and Stephan-Otto Attolini, C. and Albà, M.M. and Muñoz, J. and Tian, T.V. and Varela, I. and Vivancos, A. and Ramón Y Cajal, S. and Muñoz, P. and Rivas, C. and Abad, M. |
| 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. |
| Keywords: | Neoplasms, Sumoylation, Ubiquitins, rho GTP-Binding Proteins |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 6840 |
| Date: | 11 November 2022 |
| Official Publication: | https://doi.org/10.1038/s41467-022-34529-6 |
| PubMed: | View item in PubMed |
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