p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB.
The tumor suppressor p53 is a transcription factor that controls cellular growth and proliferation. p53 targets include RNA polymerase (pol) III-dependent genes encoding untranslated RNAs such as tRNA and 5S rRNA. These genes are repressed through interaction of p53 with TFIIIB, a TATA-binding protein (TBP)-containing factor. Although many studies have shown that p53 binds to TBP, the significance of this interaction has remained elusive. Here we demonstrate that the TBP-p53 interaction is of functional importance for regulating RNA pol III-transcribed genes. Unlike RNA pol II-dependent promoter repression, overexpressing TBP can reverse inhibition of tRNA gene transcription by p53. p53 does not disrupt the direct interaction between the TFIIIB subunits TBP and Brf1, but prevents the association of Brf1 complexes with TFIIIC2 and RNA pol III. Using chromatin immunoprecipitation assays, we found that TFIIIB occupancy on tRNA genes markedly decreases following p53 induction, whereas binding of TFIIIC2 to these genes is unaffected. Together our results support the idea that p53 represses RNA pol III transcription through direct interactions with TBP, preventing promoter occupancy by TFIIIB.
Crighton
Diane
D
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK.
Woiwode
Annette
A
Zhang
Cheng
C
Mandavia
Nihar
N
Morton
Jennifer P
JP
Warnock
Lorna J
LJ
Milner
Jo
J
White
Robert J
RJ
Johnson
Deborah L
DL
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism*; D035361:Transcription Factor TFIIIB / Q000235:genetics / Q000378:metabolism*; D019474:Transcription Factors, TFIII / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000098832:Transcription Factor TFIIIC
C090956:BRF1 protein, S cerevisiae; C441028:BRF1 protein, human; D004273:DNA, Neoplasm; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D019474:Transcription Factors, TFIII; D016159:Tumor Suppressor Protein p53; D000098832:Transcription Factor TFIIIC; D012320:RNA Polymerase III