p53 is a general repressor of RNA polymerase III transcription.
p53 is a major tumour suppressor that is inactivated in a large proportion of human cancers. We show that p53 serves as a general repressor of transcription by RNA polymerase (pol) III. It can inhibit the synthesis of a range of essential small cellular RNAs including tRNA, 5S rRNA and U6 snRNA, as well as viral products such as the adenovirus VAI RNA. Fibroblasts derived from p53 knock-out mice display a substantial increase in pol III transcriptional activity. Endogenous cellular p53 is shown to interact with the TATA-binding protein (TBP)-containing general factor TFIIIB, thereby compromising its function severely. However, assembly of TFIIIB into a pre-initiation complex confers substantial protection against the inhibitory effects of p53. Since TFIIIB is an essential determinant of the biosynthetic capacity of cells, its release from repression by p53 may contribute to a loss of growth control during the development of many tumours.
Cairns
C A
CA
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow, G12 8QQ, UK.
White
R J
RJ
D016475:3T3 Cells; D000818:Animals; D004794:Enzyme Repression / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology; D016158:Genes, p53 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D012320:RNA Polymerase III / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D012320:RNA Polymerase III