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Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.
Fong, Jia Yi; Pignata, Luca; Goy, Pierre-Alexis; Kawabata, Kimihito Cojin; Lee, Stanley Chun-Wei; Koh, Cheryl M; Musiani, Daniele; Massignani, Enrico; Kotini, Andriana G; Penson, Alex; Wun, Cheng Mun; Shen, Yudao; Schwarz, Megan; Low, Diana Hp; Rialdi, Alexander; Ki, Michelle; Wollmann, Heike; Mzoughi, Slim; Gay, Florence; Thompson, Christine; Hart, Timothy; Barbash, Olena; Luciani, Genna M; Szewczyk, Magdalena M; Wouters, Bas J; Delwel, Ruud; Papapetrou, Eirini P; Barsyte-Lovejoy, Dalia; Arrowsmith, Cheryl H; Minden, Mark D; Jin, Jian; Melnick, Ari; Bonaldi, Tiziana; Abdel-Wahab, Omar; Guccione, Ernesto.
Afiliación
  • Fong JY; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119077, Singapore.
  • Pignata L; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
  • Goy PA; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
  • Kawabata KC; Departments of Medicine and Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.
  • Lee SC; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Koh CM; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • Musiani D; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20146 Milan, Italy.
  • Massignani E; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20146 Milan, Italy.
  • Kotini AG; Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Penson A; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Wun CM; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • Shen Y; Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Schwarz M; Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Low DH; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • Rialdi A; Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Ki M; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Wollmann H; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • Mzoughi S; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • Gay F; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • Thompson C; Epigenetics Research Unit, GlaxoSmithKline, Collegeville, PA 19426, USA.
  • Hart T; Epigenetics Research Unit, GlaxoSmithKline, Collegeville, PA 19426, USA.
  • Barbash O; Epigenetics Research Unit, GlaxoSmithKline, Collegeville, PA 19426, USA.
  • Luciani GM; Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Szewczyk MM; Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Wouters BJ; Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA; Department of Hematology, Erasmus University Medical Center, 3015 GD Rotterdam, Netherlands.
  • Delwel R; Department of Hematology, Erasmus University Medical Center, 3015 GD Rotterdam, Netherlands.
  • Papapetrou EP; Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Barsyte-Lovejoy D; Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Arrowsmith CH; Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
  • Minden MD; Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
  • Jin J; Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Melnick A; Departments of Medicine and Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.
  • Bonaldi T; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20146 Milan, Italy.
  • Abdel-Wahab O; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: abdelwao@mskcc.org.
  • Guccione E; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; Department of Oncological Sciences and Tisch
Cancer Cell ; 36(2): 194-209.e9, 2019 08 12.
Article en En | MEDLINE | ID: mdl-31408619
Cancer-associated mutations in genes encoding RNA splicing factors (SFs) commonly occur in leukemias, as well as in a variety of solid tumors, and confer dependence on wild-type splicing. These observations have led to clinical efforts to directly inhibit the spliceosome in patients with refractory leukemias. Here, we identify that inhibiting symmetric or asymmetric dimethylation of arginine, mediated by PRMT5 and type I protein arginine methyltransferases (PRMTs), respectively, reduces splicing fidelity and results in preferential killing of SF-mutant leukemias over wild-type counterparts. These data identify genetic subsets of cancer most likely to respond to PRMT inhibition, synergistic effects of combined PRMT5 and type I PRMT inhibition, and a mechanistic basis for the therapeutic efficacy of PRMT inhibition in cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína-Arginina N-Metiltransferasas / Pirroles / ARN Neoplásico / Leucemia Mieloide Aguda / Empalme del ARN / Inhibidores Enzimáticos / Etilenodiaminas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína-Arginina N-Metiltransferasas / Pirroles / ARN Neoplásico / Leucemia Mieloide Aguda / Empalme del ARN / Inhibidores Enzimáticos / Etilenodiaminas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos