TAILIEUCHUNG - Báo cáo khoa học: p53-induced inhibition of protein synthesis is independent of apoptosis

Activation of a temperature-sensitive formof p53 inmurine erythroleukaemia cells results in a rapid impairment of protein synthesis that precedes inhibitionof cell proliferation and loss of cell viability by several hours. The inhibition of translation is associated with specific cleavages of polypep-tide chain initiation factors eIF4GI and eIF4B, a pheno-menon previously observed in cells induced to undergo apoptosis in response to other stimuli. | Eur. J. Biochem. 270 3122-3132 2003 FEBS 2003 doi p53-induced inhibition of protein synthesis is independent of apoptosis Constantina Constantinou1 Martin Bushell1 Ian W. Jeffrey1 Vivienne Tilleray1 Matthew West1 Victoria Frost2f Jack Hensold3 and Michael J. Clemens1 1 Translational Control Group Department of Basic Medical Sciences St George s Hospital Medical School Cranmer Terrace London 2Biochemistry Group School of Biological Sciences University of Sussex Falmer Brighton UK 3Department of Hematology and Oncology Case Western Reserve University and the Veterans Administration Cleveland Ohio USA Activation of a temperature-sensitive form of p53 in murine erythroleukaemia cells results in a rapid impairment of protein synthesis that precedes inhibition of cell proliferation and loss of cell viability by several hours. The inhibition of translation is associated with specific cleavages of polypeptide chain initiation factors eIF4GI and eIF4B a phenomenon previously observed in cells induced to undergo apoptosis in response to other stimuli. Although caspase activity is enhanced in the cells in which p53 is activated both the effects on translation and the cleavages of the initiation factors are completely resistant to inhibition of caspase activity. Moreover exposure of the cells to a combination of the caspase inhibitor and the survival factor erythropoietin prevents p53-induced cell death but does not reverse the inhibition of protein synthesis. We conclude that the p53-regulated cleavages of eIF4GI and eIF4B as well as the overall inhibition of protein synthesis are caspase-independent events that can be dissociated from the induction of apoptosis per se. Keywords caspases erythroleukaemia p53 protein synthesis temperature-sensitive mutants. The tumour suppressor protein p53 is a key regulator of both cell cycle progression and cell death by apoptosis 1-5 . Inactivating mutations of p53 have been found with high .

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