title: Regulation of protein synthesis by inducible wild-type p53 in human lung carcinoma cells.
abstract: Activation of an over-expressed mutant form of the tumour suppressor protein p53 has been shown to inhibit protein synthesis. To determine whether this effect is due only to high level expression or the mutant nature of the protein, we have used a doxycycline-inducible lung carcinoma cell line capable of expressing wild-type p53. We now show that levels of wild-type p53 similar to those expressed endogenously also inhibit protein synthesis. The mechanism involves dephosphorylation and accumulation of the translational inhibitor 4E-BP1, and increased association of 4E-BP1 with initiation factor eIF4E. The inhibition of translation is not a consequence of p53-mediated apoptosis.
authors.affiliation: Translational Control Group, Centre for Molecular and Metabolic Signalling, Division of Basic Medical Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Vivienne
authors.initials: V
authors.lastname: Tilleray
authors.forename: Constantina
authors.initials: C
authors.lastname: Constantinou
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clemens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D004318:Doxycycline; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D004318:Doxycycline