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.

Publication DOI: https://doi.org/10.1093/nar/gkm208
Divisions: College of Health & Life Sciences > Aston Medical School
Funding Information: The authors are grateful to Gordon Peters for NARF2 and E6-NARF2 cell lines. This work was funded by the Wellcome Trust and Cancer Research UK. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.
Additional Information: © 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: Genetics
Publication ISSN: 1362-4962
Last Modified: 08 Dec 2023 10:48
Date Deposited: 15 Nov 2018 09:10
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2007-05-01
Authors: Morton, Jennifer P.
Kantidakis, Theodoros (ORCID Profile 0000-0002-3515-5235)
White, Robert J.


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