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Your search keyword '"John S. Reece-Hoyes"' showing total 3 results
Start Over Author "John S. Reece-Hoyes" Journal nature chemical biology
3 results on '"John S. Reece-Hoyes"'

1. Author Correction: CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing’s sarcoma

Author

Kevin Xie, Favour A Akinjiyan, Frederic Sigoillot, John A. Tallarico, Jeffrey A. Chao, Judith Knehr, Eric T Williams, Matthew T. Spencer, Juan B. Rodríguez-Molina, Gregory A. Michaud, Walter Carbone, Howard R Miller, Aleem Fazal, Sarah H. Carl, Jeremy L. Jenkins, Jason Murphy, Jonathan J. Turner, Gregory J Molind, Guglielmo Roma, Felix Lohmann, Caroline G Artus-Revel, Scott Gleim, Wilhelm A. Weihofen, Aye Chen, Michael Salcius, Rohan Eric John Beckwith, John S. Reece-Hoyes, Scott M. Brittain, Nathan T. Ross, Mark Zambrowski, Geoffrey Boynton, Lori A. Passmore, Min Jia, Elizabeth George, Sven Schuierer, Chitra Saran, Martin Henault, Markus Schirle, Jason R. Thomas, Seth Carbonneau, Yuan Wang, and Johannes H Wilbertz

Subjects
Oncology, medicine.medical_specialty, business.industry, Node (networking), Druggability, Ewing's sarcoma, Cell Biology, medicine.disease, Text mining, Internal medicine, medicine, business, Molecular Biology, Pre mrna processing
Published
2020
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2. CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma

Author

Rohan Eric John Beckwith, John A. Tallarico, Geoffrey Boynton, Jason R. Thomas, Gregory J Molind, Scott M. Brittain, Lori A. Passmore, Min Jia, Michael Salcius, Jason Murphy, Jonathan J. Turner, Seth Carbonneau, John S. Reece-Hoyes, Juan B. Rodríguez-Molina, Judith Knehr, Howard R Miller, Scott Gleim, Yuan Wang, Sven Schuierer, Martin Henault, Frederic Sigoillot, Johannes H Wilbertz, Walter Carbone, Felix Lohmann, Aye Chen, Chitra Saran, Aleem Fazal, Favour A Akinjiyan, Gregory A. Michaud, Jeremy L. Jenkins, Sarah H. Carl, Eric T Williams, Matthew T. Spencer, Guglielmo Roma, Wilhelm A. Weihofen, Elizabeth George, Markus Schirle, Kevin Xie, Mark Zambrowski, Jeffrey A. Chao, Caroline G Artus-Revel, and Nathan T. Ross

Subjects
Male, Cell Survival, Phenotypic screening, Phenylalanine, Druggability, Apoptosis, Cleavage and polyadenylation specificity factor, Sarcoma, Ewing, Biology, Article, Mass Spectrometry, Piperazines, 03 medical and health sciences, Mice, Cell Line, Tumor, medicine, RNA Precursors, Animals, Humans, RNA, Messenger, RNA, Small Interfering, Molecular Biology, 030304 developmental biology, 0303 health sciences, Binding Sites, 030302 biochemistry & molecular biology, Cleavage And Polyadenylation Specificity Factor, Ewing's sarcoma, Myeloid leukemia, Cell Biology, medicine.disease, Mice, Inbred C57BL, Leukemia, Leukemia, Myeloid, Acute, HEK293 Cells, Phenotype, Cancer research, Sarcoma, Chemical genetics, Carboxylic Ester Hydrolases, Neoplasm Transplantation, Protein Binding
Abstract

The post-genomic era has seen many advances in our understanding of cancer pathways, yet resistance and tumor heterogeneity necessitate multiple approaches to target even monogenic tumors. Here, we combine phenotypic screening with chemical genetics to identify pre-mRNA endonuclease Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) as the target of JTE-607, a small molecule with previously unknown target. We show that CPSF3 represents a novel synthetic lethal node in a sub-set of acute myeloid leukemia (AML) and Ewing’s sarcoma cancer cell lines. Inhibition of CPSF3 by JTE-607 alters expression of known downstream effectors in AML and Ewing’s sarcoma lines, upregulates apoptosis and causes tumor-selective stasis in mouse xenografts. Mechanistically, it prevents the release of newly synthesized pre-mRNAs, resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. This study implicates pre-mRNA processing, and specifically CPSF3, as a druggable target providing a new avenue to therapeutic intervention in cancer.

Published
2018

3. Discovery of a ZIP7 inhibitor from a Notch pathway screen

Author

Owen Wallace, Zhao B. Kang, Jian Ding, Abhishek Dogra, Jeremy L. Jenkins, Joseph Loureiro, Christophe Antczak, Sven Schuierer, John A. Tallarico, Rishi K. Jain, Geoff Boynton, Amy Chen, Scott M. Brittain, Richard I. McDonald, Christy Fryer, Jian Shao, Frederic Sigoillot, Sara Gans, Jeffery A. Porter, Kayla Tyskiewicz, Dominic Hoepfner, Markus Schirle, Erin Nolin, Wilhelm A. Weihofen, Martin Beibel, Jason R. Thomas, Paula Bernasconi-Elias, Elizabeth George, Ning Guo, Guglielmo Roma, Alicia Lindeman, Amy E. Palmer, Yi Yang, Bushell Simon, Luis Llamas, Haibing Guo, Kevin Xie, Stephen M. Canham, Samuel B. Ho, Kyle P. Carter, Nicolette Guthrie, Somnath Bandyopadhyay, and John S. Reece-Hoyes

Subjects
Cell signaling, Phenotypic screening, Notch signaling pathway, Apoptosis, medicine.disease_cause, Endoplasmic Reticulum, Article, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, Receptor, Notch1, Molecular Biology, Cation Transport Proteins, 030304 developmental biology, 0303 health sciences, Mutation, biology, Chemistry, Endoplasmic reticulum, 030302 biochemistry & molecular biology, Cell Biology, Endoplasmic Reticulum Stress, Transport protein, Cell biology, Protein Transport, Zinc, Cell Transformation, Neoplastic, biology.protein, Signal transduction, SLC39A7, Carrier Proteins, Signal Transduction
Abstract

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling. Generation and sequencing of a compound-resistant cell line identified a V430E mutation in ZIP7 that confers transferable resistance to the compound NVS-ZP7-4. NVS-ZP7-4 altered zinc in the ER, and an analog of the compound photoaffinity labeled ZIP7 in cells, suggesting a direct interaction between the compound and ZIP7. NVS-ZP7-4 is the first reported chemical tool to probe the impact of modulating ER zinc levels and investigate ZIP7 as a novel druggable node in the Notch pathway.

Published
2018

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