Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53.
Megan J. Bywater,Gretchen Poortinga,Gretchen Poortinga,Elaine Sanij,Elaine Sanij,Nadine Hein,Abigail Peck,Carleen Cullinane,Meaghan Wall,Leonie A. Cluse,Denis Drygin,Kenna Anderes,Nanni Huser,Chris Proffitt,Josh Bliesath,Mustapha Haddach,Michael K. Schwaebe,David M. Ryckman,William G. Rice,Clemens A. Schmitt,Clemens A. Schmitt,Scott W. Lowe,Ricky W. Johnstone,Ricky W. Johnstone,Richard B. Pearson,Grant A. McArthur,Ross D. Hannan +26 more
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It is shown that rDNA transcription can be therapeutically targeted with the small molecule CX-5461 to selectively kill B-lymphoma cells in vivo while maintaining a viable wild-type B cell population.About:
This article is published in Cancer Cell.The article was published on 2012-07-10 and is currently open access. It has received 475 citations till now. The article focuses on the topics: RNA polymerase II & Transcription (biology).read more
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Targeting the translation machinery in cancer
Mamatha Bhat,Nathaniel Robichaud,Laura Hulea,Nahum Sonenberg,Jerry Pelletier,Ivan Topisirovic +5 more
TL;DR: The role of translation in cancer is discussed, with a particular focus on the eIF4F (eukaryotic translation initiation factor 4F) complex, and an overview of recent efforts aiming to 'translate' these results to the clinic is provided.
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Ribosomal proteins: functions beyond the ribosome
TL;DR: The current understanding of how ribosomal stress provokes the accumulation of ribosome-free Ribosomal proteins, as well as the ribosomesome-independent functions of ribOSomal proteins in tumorigenesis, immune signaling, and development are overviewed.
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An overview of pre‐ribosomal RNA processing in eukaryotes
Anthony K. Henras,Célia Plisson-Chastang,Marie-Françoise O'Donohue,Anirban Chakraborty,Pierre-Emmanuel Gleizes +4 more
TL;DR: A consensus scheme of pre‐ribosomal RNA maturation is emerging from studies in various kinds of eukaryotic organisms, including small nucleolar ribonucleoparticles, but major differences between mammalian and yeast pre-ribosome RNA processing have recently come to light.
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Ribosome biogenesis in cancer: new players and therapeutic avenues
TL;DR: The most recent findings that provide new insights into the molecular basis of ribosome biogenesis in cancer are highlighted and the perspective on how these observations present opportunities for the design of new targeted cancer treatments is offered.
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CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.
Hong Xu,Marco Di Antonio,Steven McKinney,Veena Mathew,Brandon Ho,Nigel J. O'Neil,Nancy Dos Santos,Jennifer Silvester,Vivien Wei,Jessica Garcia,Farhia Kabeer,Daniel Lai,Priscilla Soriano,Judit P. Banáth,Derek S. Chiu,Damian Yap,Daniel D. Le,Frank B Ye,Anni Zhang,Kelsie L. Thu,John Soong,Shu chuan Lin,Angela Hsin Chin Tsai,Tomo Osako,Teresa Ruiz de Algara,Darren N. Saunders,Jason Wong,Jian Xian,Marcel B. Bally,James D. Brenton,Grant W. Brown,Sohrab P. Shah,David W. Cescon,David W. Cescon,Tak W. Mak,Carlos Caldas,Peter C. Stirling,Phil Hieter,Shankar Balasubramanian,Samuel Aparicio +39 more
TL;DR: CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition.
References
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The c- myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
Jerry M. Adams,A W Harris,Carl A. Pinkert,Lynn M. Corcoran,Warren S. Alexander,Suzanne Cory,Richard D. Palmiter,Ralph L. Brinster +7 more
TL;DR: Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin μ or κ enhancer frequently develop a fatal lymphoma within a few months of birth and constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation.
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The multifunctional nucleolus
TL;DR: Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now show that it has additional functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response and biogenesis of multiple ribonucleoprotein particles.
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The c-Myc target gene network.
TL;DR: Both genomic and functional analyses of c-Myc targets suggest that while c- myc behaves as a global regulator of transcription, groups of genes involved in cell cycle regulation, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function are over-represented in the c-myc target gene network.
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Does the ribosome translate cancer
TL;DR: Although many studies have correlated deregulation of protein biosynthesis with cancer, it remains to be established whether this translates directly into an increase in cancer susceptibility, and under what circumstances.
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The Nucleolus under Stress
TL;DR: Nucleolar function in the stress-induced regulation of p53 and the specific changes in nucleolar morphology and composition that occur upon stress are reviewed.