| Autor: |
Sofia Lachiondo-Ortega, Claudia M. Rejano-Gordillo, Jorge Simon, Fernando Lopitz-Otsoa, Teresa C. Delgado, Krystyna Mazan-Mamczarz, Naroa Goikoetxea-Usandizaga, L. Estefanía Zapata-Pavas, Ana García-del Río, Pietro Guerra, Patricia Peña-Sanfélix, Natalia Hermán-Sánchez, Ruba Al-Abdulla, Carmen Fernandez-Rodríguez, Mikel Azkargorta, Alejandro Velázquez-Cruz, Joris Guyon, César Martín, Juan Diego Zalamea, Leire Egia-Mendikute, Arantza Sanz-Parra, Marina Serrano-Maciá, Irene González-Recio, Monika Gonzalez-Lopez, Luis Alfonso Martínez-Cruz, Patrizia Pontisso, Ana M. Aransay, Rosa Barrio, James D. Sutherland, Nicola G.A. Abrescia, Félix Elortza, Amaia Lujambio, Jesus M. Banales, Raúl M. Luque, Manuel D. Gahete, Asís Palazón, Matias A. Avila, Jose J. G. Marin, Supriyo De, Thomas Daubon, Antonio Díaz-Quintana, Irene Díaz-Moreno, Myriam Gorospe, Manuel S. Rodríguez, María Luz Martínez-Chantar |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 43, Iss 3, Pp 113924- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.113924 |
| Popis: |
Summary: The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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