Targeting RNA polymerase I transcription and the nucleolus for cancer therapy

Hannan, Ross D., Drygin, Denis and Pearson, Richard B. (2013) Targeting RNA polymerase I transcription and the nucleolus for cancer therapy. Expert Opinion on Therapeutic Targets, 17 8: 873-878. doi:10.1517/14728222.2013.818658


Author Hannan, Ross D.
Drygin, Denis
Pearson, Richard B.
Title Targeting RNA polymerase I transcription and the nucleolus for cancer therapy
Journal name Expert Opinion on Therapeutic Targets   Check publisher's open access policy
ISSN 1472-8222
1744-7631
Publication date 2013-08
Sub-type Editorial
DOI 10.1517/14728222.2013.818658
Volume 17
Issue 8
Start page 873
End page 878
Total pages 6
Place of publication London, United Kingdom
Publisher Informa Healthcare
Collection year 2014
Language eng
Formatted abstract
The nucleoli are the site of the production of ribosomes, the protein synthetic apparatus of the cell. The presence of enlarged nucleoli, reflecting increased ribosomal gene transcription, has long been used by pathologists as an indicator of aggressive tumors. However, over the last 10 years a growing body of evidence has revealed that the nucleolus contains a dynamic cohort of over 4500 proteins, the majority of which have no function in ribosome production. The activity of some of these proteins is modulated by their regulated sequestration and release from the nucleolus. In particular, the nucleolus plays a central role in sensing cellular stress to modulate the abundance of the critical tumor suppressor protein p53. The finding that p53 activity is dysregulated in up to 50% of all human cancers highlights the importance of the nucleolar stress response in limiting malignant transformation. The development of drugs to selectively inhibit transcription of the ribosomal RNA genes in the nucleolus has paved the way for a new therapeutic approach to hijack nucleolar stress to selectively and non-genotoxically activate p53 in tumor cells. Here, we describe the potential application of this exciting new class of drugs for the treatment of human cancer.
Keyword 5-FU
Actinomycin D
CX-5461
MDM2
Nucleolar stress
Nucleolar surveillance
p53
Ribosomal RNA
RNA polymerase I transcription
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Editorial
Collections: Non HERDC
School of Biomedical Sciences Publications
 
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