Direct regulation of RNA polymerase III transcription by RB, p53 and c-Myc.

Abstract

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.

• Authors: Zoë A Felton-Edkins, Niall S Kenneth, Timothy R P Brown, Nicole L Daly, Natividad Gomez-Roman, Carla Grandori, Robert N Eisenman, Robert J White
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) 2003 May-Jun Vol. 2 Issue 3 Pg. 181-4 ISSN: 1538-4101 [Print] United States
• PMID: 12734418 (Publication Type: Journal Article, Review)

Chemical References

• MAS1 protein, human
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-myc
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• RNA
• DNA Polymerase III

Topics

• Animals
• Cell Division (genetics)
• Cell Transformation, Neoplastic (genetics, metabolism)
• DNA Polymerase III (genetics, metabolism)
• Eukaryotic Cells (enzymology)
• Humans
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• RNA (genetics)
• Retinoblastoma Protein (genetics, metabolism)
• Transcription, Genetic (genetics)
• Tumor Suppressor Protein p53 (genetics, metabolism)