Journal article

The nucleolus as a fundamental regulator of the p53 response and a new target for cancer therapy

Simone J Woods, Katherine M Hannan, Richard B Pearson, Ross D Hannan

BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS | ELSEVIER SCIENCE BV | Published : 2015

Abstract

BACKGROUND: Recent studies have highlighted the fundamental role that key oncogenes such as MYC, RAS and PI3K occupy in driving RNA Polymerase I transcription in the nucleolus. In addition to maintaining essential levels of protein synthesis, hyperactivated ribosome biogenesis and nucleolar function plays a central role in suppressing p53 activation in response to oncogenic stress. Consequently, disruption of ribosome biogenesis by agents such as the small molecule inhibitor of RNA Polymerase I transcription, CX-5461, has shown unexpected, potent, and selective effects in killing tumour cells via disruption of nucleolar function leading to activation of p53, independent of DNA damage. SCOPE ..

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