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lüll Distinct roles of MDMX in the regulation of p53 response to ribosomal stress Gilkes DM; Chen JCell Cycle 2007[Jan]; 6 (2): 151-5Approximately 50% of protein and RNA synthesis in proliferating cells are devoted to ribosomal biogenesis. Coordination between ribosome biogenesis, growth, and proliferation is critical for maintenance of homeostasis and tumor suppression. Aberrant rRNA expression and processing is sensed by p53. Ribosomal stress increases the binding between MDM2 and ribosomal proteins L5, L11, and L23, resulting in p53 stabilization. Our recent study showed that p53 activation by ribosomal stress also involves degradation of MDMX in an MDM2-dependent fashion. Failure to eliminate MDMX due to overexpression results in the sequestration of p53 into inactive complexes, severely impairing p53-dependent cell cycle arrest during ribosomal stress. Furthermore, MDMX overexpression promotes resistance to the chemotherapeutic agent 5-FU, which at low concentrations activates p53 by inhibiting RNA metabolism. Therefore, MDMX is an important regulator of p53 response to ribosomal stress. MDMX overexpression in tumors may significantly influence response to chemotherapy agents that target rRNA biogenesis.|Animals[MESH]|Humans[MESH]|Oxidative Stress/genetics/*physiology[MESH]|Proto-Oncogene Proteins c-mdm2/biosynthesis/genetics/*physiology[MESH]|Ribosomes/genetics/*metabolism/physiology[MESH]|Tumor Suppressor Protein p53/*metabolism/physiology[MESH] |