Ahmed El Motiam – Role of protein SUMOylation 🗓 🗺
Role of protein SUMOylation in the regulation of oncogenic and tumor suppressor proteins
The Small Ubiquitin like Modifier (SUMO) is regulating many key pathways in the cell including those acting on tumor suppressors and oncogenic proteins.
Here we analyzed the impact of SUMO on the RPL11-Mdm2-p53 signaling. We show that SUMO covalently modify the tumor suppressor protein RPL11. Interestingly, 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 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 oncogenic stress.
Also, we analyzed the impact of SUMO on regulation of the oncogenic RAS activity. We show that RAS is modified by SUMO covalently and non-covalently as well. Interestingly SUMOylation of RAS is negatively regulating RAS protein in inducing Senescence in MCF-7 cells.
Collectively, our data identify SUMO protein conjugation to RPL11 as a new regulator of the p53-mediated cellular response to different types of stress, in addition that SUMO decreases the oncogenic capacity of RAS.
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