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Merck
  • SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer.

SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer.

Cell reports (2024-03-20)
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
摘要

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.

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Roche
不含EDTA的cOmplete Mini蛋白酶抑制剂混合物, Protease Inhibitor Cocktail Tablets provided in a glass vial, Tablets provided in a glass vial
Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
毒胡萝卜素, ≥98% (HPLC), solid film