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A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. | LitMetric

A targeting modality for destruction of RNA polymerase I that possesses anticancer activity.

Cancer Cell

Molecular Cancer Biology Program and Centre for Drug Research, University of Helsinki, Helsinki 00014, Finland; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address:

Published: January 2014

AI Article Synopsis

Article Abstract

We define the activity and mechanisms of action of a small molecule lead compound for cancer targeting. We show that the compound, BMH-21, has wide and potent antitumorigenic activity across NCI60 cancer cell lines and represses tumor growth in vivo. BMH-21 binds GC-rich sequences, which are present at a high frequency in ribosomal DNA genes, and potently and rapidly represses RNA polymerase I (Pol I) transcription. Strikingly, we find that BMH-21 causes proteasome-dependent destruction of RPA194, the large catalytic subunit protein of Pol I holocomplex, and this correlates with cancer cell killing. Our results show that Pol I activity is under proteasome-mediated control, which reveals an unexpected therapeutic opportunity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930145PMC
http://dx.doi.org/10.1016/j.ccr.2013.12.009DOI Listing

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