RNA polymerase III transcription and cancer.
RNA polymerase (pol) III synthesizes a range of essential products, including tRNA, 5S rRNA and 7SL RNA, which are required for protein synthesis and trafficking. High rates of pol III transcription are necessary for cells to sustain growth. A wide range of transformed and tumour cell types have been shown to express elevated levels of pol III products. This review will summarize what is known about the mechanisms responsible for this deregulation. Some transforming agents have been shown to stimulate expression of the pol III-specific transcription factors TFIIIB or TFIIIC2. In addition, TFIIIB is bound and activated by several oncogenic proteins, including c-Myc. Conversely, TFIIIB interacts in healthy cells with the tumour suppressors RB and p53. Indeed, the ability to limit pol III transcription through TFIIIB may contribute to their growth-suppression capacities. The function of p53 and/or RB is compromised in most if not all transformed cells; the resultant derepression of TFIIIB may provide an almost universal route to deregulate pol III transcription in cancers. In addition to effects on protein synthesis and growth, there is a precedent for a pol III product having oncogenic activity.
White
Robert J
RJ
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Davidson Building, Glasgow G12 8QQ, UK. rwhite@udcf.gla.ac.uk
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000209:etiology; D012318:RNA Polymerase I / Q000235:genetics; D012320:RNA Polymerase III / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000502:physiology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D012318:RNA Polymerase I; D012320:RNA Polymerase III