Regulation of the RP-MDM2-P53 pathway by SUMO
- Autores: Ahmed El Motiam
- Directores de la Tesis: Carmen Rivas Vázquez (dir. tes.), Manuel Collado Rodríguez (codir. tes.)
- Lectura: En la Universidade de Santiago de Compostela ( España ) en 2019
- Idioma: inglés
- Tribunal Calificador de la Tesis: Ignacio Palmero Rodríguez (presid.), Susana Llanos Girón (secret.), Rune Matthiesen (voc.)
- Programa de doctorado: Programa de Doctorado en Medicina Molecular por la Universidad de Santiago de Compostela
- Materias:
- Enlaces
- Tesis en acceso abierto en: MINERVA
- Resumen
The ribosomal protein L11 integrate different types of stress into a p53-mediated response. Here we analyzed the impact of the ubiquitin-like protein SUMO on the RPL11-MDM2-p53 signaling. We show that SUMO modify RPL11, mutation of all lysine residues in RPL11 did not abolish SUMOylation, suggesting that this conjugation occurs through an alternative non-canonical SUMOylation pathway. We find that SUMO downregulates the conjugation of the ubiquitin-like protein NEDD8 to RPL11 and promotes the translocation of RPL11 outside of the nucleoli. Moreover, the SUMO conjugating enzyme, Ubc9, is required for RPL11-mediated activation of p53. SUMOylation of RPL11 is triggered by ribosomal stress as well as by ARF. The ribosomal protein L23 and ARF can be also modulated by SUMO. In addition, this study has led us to advance in the knowledge of post-translational modifications by ubiquitin-like proteins demonstrating that SUMO can bind to a substrate in lysine independent manner and that there is an interplay between SUMOylation and NEDDylation.
