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Cyclin C is a haploinsufficient tumour suppressor.
Li, Na; Fassl, Anne; Chick, Joel; Inuzuka, Hiroyuki; Li, Xiaoyu; Mansour, Marc R; Liu, Lijun; Wang, Haizhen; King, Bryan; Shaik, Shavali; Gutierrez, Alejandro; Ordureau, Alban; Otto, Tobias; Kreslavsky, Taras; Baitsch, Lukas; Bury, Leah; Meyer, Clifford A; Ke, Nan; Mulry, Kristin A; Kluk, Michael J; Roy, Moni; Kim, Sunkyu; Zhang, Xiaowu; Geng, Yan; Zagozdzon, Agnieszka; Jenkinson, Sarah; Gale, Rosemary E; Linch, David C; Zhao, Jean J; Mullighan, Charles G; Harper, J Wade; Aster, Jon C; Aifantis, Iannis; von Boehmer, Harald; Gygi, Steven P; Wei, Wenyi; Look, A Thomas; Sicinski, Piotr.
Afiliação
  • Li N; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Fassl A; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Chick J; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Inuzuka H; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Li X; 1] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Mansour MR; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA [3] Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA [4] Department of Haem
  • Liu L; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Wang H; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • King B; Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.
  • Shaik S; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Gutierrez A; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA [3] Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Ordureau A; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Otto T; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Kreslavsky T; 1] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Baitsch L; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Bury L; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Meyer CA; 1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Harvard School of Public Health, Boston, Massachusetts 02115, USA.
  • Ke N; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Mulry KA; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Kluk MJ; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Roy M; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Kim S; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA.
  • Zhang X; Cell Signaling Technology, Inc., Danvers, Massachusetts 01923, USA.
  • Geng Y; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Zagozdzon A; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Jenkinson S; Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK.
  • Gale RE; Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK.
  • Linch DC; Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK.
  • Zhao JJ; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Mullighan CG; Department of Pathology, St. Jude Research Hospital, Memphis, Tennessee 38105, USA.
  • Harper JW; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Aster JC; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Aifantis I; Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.
  • von Boehmer H; 1] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Wei W; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Look AT; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA [3] Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Sicinski P; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Cell Biol ; 16(11): 1080-91, 2014 Nov.
Article em En | MEDLINE | ID: mdl-25344755
Cyclin C was cloned as a growth-promoting G1 cyclin, and was also shown to regulate gene transcription. Here we report that in vivo cyclin C acts as a haploinsufficient tumour suppressor, by controlling Notch1 oncogene levels. Cyclin C activates an 'orphan' CDK19 kinase, as well as CDK8 and CDK3. These cyclin-C-CDK complexes phosphorylate the Notch1 intracellular domain (ICN1) and promote ICN1 degradation. Genetic ablation of cyclin C blocks ICN1 phosphorylation in vivo, thereby elevating ICN1 levels in cyclin-C-knockout mice. Cyclin C ablation or heterozygosity collaborates with other oncogenic lesions and accelerates development of T-cell acute lymphoblastic leukaemia (T-ALL). Furthermore, the cyclin C encoding gene CCNC is heterozygously deleted in a significant fraction of human T-ALLs, and these tumours express reduced cyclin C levels. We also describe point mutations in human T-ALL that render cyclin-C-CDK unable to phosphorylate ICN1. Hence, tumour cells may develop different strategies to evade inhibition by cyclin C.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinases Ciclina-Dependentes / Receptor Notch1 / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Ciclina C Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinases Ciclina-Dependentes / Receptor Notch1 / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Ciclina C Idioma: En Ano de publicação: 2014 Tipo de documento: Article