SURF2 is a MDM2 antagonist in triggering the nucleolar stress response

Cancer cells are addicted to strong ribosome production to sustain their proliferation rate. Many chemotherapies impede ribosome production which is perceived by cells as "nucleolar stress" (NS), triggering p53-dependent and independent response pathways leading to cell cycle arrest and/or apoptosis. The 5S RNP particle, a sub-ribosomal particle, is instrumental to NS response. Upon ribosome assembly defects, the 5S RNP accumulate as free form. This free form is able to sequester and inhibit MDM2, thus promoting p53 stabilization. To investigate how cancer cells can resist to NS, we purified free-5S RNP and uncovered a new interaction partner, SURF2. Functional characterization of SURF2 shows that its depletion increases cellular sensitivity to NS, while its overexpression promotes their resistance to it. Consistently, SURF2 expression level negatively correlates with the overall survival in adrenocortical and head and neck squamous cell carcinomas. Our data demonstrate that SURF2 buffers free-5S RNP particles, and can modulate their activity. SURF2 regulates NS responses, and is a key player in both ribosomopathies and oncogenic mechanisms. here we investigated the effect of SURF2 depletion (siSURF2) in U2OS cells compared to control (siSCR). Cells where treated twice with siRNAs at 48H inteval and after 96 hours cells were pelleted and RNA extracted using Trizol extraxtion method. 3 biological replicates were compared (siSCR-1, sSCR-2, siSCR-3 vs siSURF2-1, siSURF2-2 and siSURF2-3).We then performed gene expression differential analysis using RNAseq approach (performed by Genewiz).