The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer.

Abstract:

:The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that inactivate tumor suppressors, hyperactivate oncogenes, and upregulate protein kinases, all of which promote Pol I transcription and drive cell proliferation. The intimate balance between Pol I transcription and growth-factor signaling is perturbed in cancer cells, indicating that upregulation of rRNA synthesis is mandatory for all tumors. Though the emerging picture of transcriptional regulation reveals an unexpected level of complexity, we are beginning to understand the multiple links between rRNA biogenesis and cancer. In this review, we discuss experimental data and potential strategies to downregulate rRNA synthesis and induce an antiproliferative response in cancer cells.

authors

Drygin D,Rice WG,Grummt I

doi

10.1146/annurev.pharmtox.010909.105844

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

131-56

eissn

0362-1642

issn

1545-4304

journal_volume

50

pub_type

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