Journal: Cells

Article Title: Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age

doi: 10.3390/cells9020266

Figure Lengend Snippet: Chemotherapeutics affecting Pol I transcription.

Article Snippet: A new chemical series of Pol I transcription inhibitors is currently under research by Pimera Inc. (personal communication).

Techniques: Activation Assay, DNA Synthesis, Inhibition, Disruption

Journal: Cells

Article Title: Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age

doi: 10.3390/cells9020266

Figure Lengend Snippet: Schematic representation of mechanisms of action of unspecific Pol I transcription inhibitors. Figure showing an overview of the effects of unspecific Pol I transcription inhibitors. Blue - Alkylating agents; Red—Antimetabolites; Green—Plant alkaloids; Purple—Antibiotics. *—DNA adducts (purple), Platinum adducts (blue) or DNA damage (red).

Article Snippet: A new chemical series of Pol I transcription inhibitors is currently under research by Pimera Inc. (personal communication).

Techniques:

Journal: Cells

Article Title: Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age

doi: 10.3390/cells9020266

Figure Lengend Snippet: Schematic representation of mechanisms of action of specific Pol I transcription inhibitors. ( A ) Mode of action of CX-3543, disruption of Nucleolin binding to G4 DNA structures. ( B ) Mode of action of CX-5461, disruption of Pol I-SL-1 interaction and an unclear role in G4 stabilization. ( C ) Mode of action of BMH-21, disruption of Pol I complex and ubiquitin-mediated proteasome degradation of POLR1A (RPS194), inhibition of transcription elongation and an unclear role in G4 stabilization.

Article Snippet: A new chemical series of Pol I transcription inhibitors is currently under research by Pimera Inc. (personal communication).

Techniques: Disruption, Binding Assay, Ubiquitin Proteomics, Inhibition

Journal: Cells

Article Title: Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age

doi: 10.3390/cells9020266

Figure Lengend Snippet: Schematic representation of the sensitization of MYC-overexpressing cancers to Pol I inhibition therapy. A cell with normal levels of MYC (left) maintains physiological levels of rRNA and RP and therefore produce adequate levels of ribosomes. Overexpression of MYC in cancer cells (right) causes increases of both rRNA and RP allowing for an increased number of ribosomes necessary to maintain uncontrolled growth and proliferation. Therapy with Pol I transcription inhibitors (top) leads to a reduction in rRNA levels while RP levels are maintained at a high level due to the effect of MYC on Pol II transcription. Excess free RP can then activate the NSP, allowing the stabilization of p53 and consequently promotes cell cycle arrest or apoptosis.

Article Snippet: A new chemical series of Pol I transcription inhibitors is currently under research by Pimera Inc. (personal communication).

Techniques: Inhibition, Over Expression