Direct regulation of RNA polymerase III transcription by RB, p53 and c-Myc.
The synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is cell cycle regulated in higher organisms. Overexpression of pol III products is a general feature of transformed cells. These observations may be explained by the fact that a pol III-specific transcription factor, TFIIIB, is strongly regulated by the tumor suppressors RB and p53, as well as the proto-oncogene product c-Myc. RB and p53 repress TFIIIB, but this restraint can be lost in tumors through a variety of mechanisms. In contrast, c-Myc binds and activates TFIIIB, causing potent induction of pol III transcription. Using chromatin immunoprecipitation and RNA interference, we show that c-Myc interacts with tRNA and 5S rRNA genes in transformed cervical cells, stimulating their expression. Availability of pol III products may be an important determinant of a cell's capacity to grow. The ability to regulate pol III output may therefore be integral to the growth control functions of RB, p53 and c-Myc.
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
Zoë A
ZA
Felton-Edkins
Niall S
NS
Kenneth
Timothy R P
TR
Brown
Nicole L
NL
Daly
Natividad
N
Gomez-Roman
Carla
C
Grandori
Robert N
RN
Eisenman
Robert J
RJ
White
D000818:Animals; D002455:Cell Division / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000201:enzymology*; D006801:Humans; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D012313:RNA; D004258:DNA Polymerase III