Journal
TRENDS IN MOLECULAR MEDICINE
Volume 19, Issue 11, Pages 643-654Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2013.07.005
Keywords
nucleolus; nucleolar stress; p53; ribosomal gene transcription; RNA polymerase I inhibitor; cancer therapy
Funding
- National Health and Medical Research Council (NHMRC) of Australia
- Leukaemia Foundation
- Prostate Cancer Foundation of Australia
- NHMRC
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For over 100 years, pathologists have utilised an increase in size and number of nucleoli, the subnuclear site of ribosome synthesis, as a marker of aggressive tumours. Despite this, the contribution of the nucleolus and ribosomal RNA synthesis to cancer has been largely overlooked. This concept has recently changed with the demonstration that the nucleolus indirectly controls numerous other cellular function's, in particular, the cellular activity of the critical tumour suppressor protein, p53. Moreover, selective inhibition of ribosomal gene transcription in the nucleolus has been shown to be an effective therapeutic strategy to promote cancer-specific activation of p53. This article reviews the largely untapped potential of the nucleolus and ribosomal gene transcription as exciting new targets for cancer therapy.
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