title: Differential transcription-coupled translational inhibition of human p53 expression: a potentially important mechanism of regulating p53 expression in normal versus tumor tissue.
abstract: p53 protein accumulation is triggered following exposure to potentially carcinogenic DNA-damaging agents and other physiological processes. Here we show that although p53 mRNA transcribed from the downstream P(1) transcription start site was the only p53 transcript detected in human cell lines and tumor specimens, p53 transcripts initiated at the upstream P(0) and P(2) start sites were primary in normal human tissues, with P(0)-initiated p53 transcripts comprising approximately 50% of total p53 transcripts. P(1)-initiated p53 mRNA was not detected in most normal human tissues examined. Decreased translational efficiency was observed for mRNAs containing p53 5' untranslated region sequences located between P(0) and P(1) in rabbit reticulocyte lysates and in cell lines; no inhibitory activity was observed for sequences located downstream of the P(1) start site. These data suggest that a transcriptional switch from P(0)-/P(2)- to P(1)-initiated p53 mRNA could be an important mechanism by which cells regulate p53 expression.
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Strudwick
authors.forename: Louis Michael
authors.initials: LM
authors.lastname: Carastro
authors.forename: Tazia
authors.initials: T
authors.lastname: Stagg
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009928:Organ Specificity; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53