RNA polymerase III transcription is repressed in response to the tumour suppressor ARF.
The tumour suppressor protein ARF provides a defence mechanism against hyperproliferative stresses that can result from the aberrant activation of oncogenes. Accordingly, ARF is silenced or deleted in many human cancers. Activation of ARF can arrest growth and cell cycle progression, or trigger apoptosis. A principle mediator of these effects is p53, which ARF stabilizes by binding and inhibiting MDM2. However, ARF has additional targets and remains able to block growth in the absence of p53, albeit less efficiently. For example, ARF can suppress rRNA production in a p53-independent manner. We have found that the synthesis of tRNA by RNA polymerase III is also inhibited in response to ARF. However, in contrast to its effects on rRNA synthesis, ARF is unable to inhibit tRNA gene transcription when p53 is ablated. These results add to the growing list of cellular changes that can be triggered by ARF induction.
Morton
Jennifer P
JP
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, UK.
Kantidakis
Theodoros
T
White
Robert J
RJ
D002460:Cell Line; D050687:E2F1 Transcription Factor / Q000378:metabolism; D006801:Humans; D012320:RNA Polymerase III / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D012320:RNA Polymerase III