Nature Communications (Oct 2019)
A kinase-independent role for CDK8 in BCR-ABL1+ leukemia
- Ingeborg Menzl,
- Tinghu Zhang,
- Angelika Berger-Becvar,
- Reinhard Grausenburger,
- Gerwin Heller,
- Michaela Prchal-Murphy,
- Leo Edlinger,
- Vanessa M. Knab,
- Iris Z. Uras,
- Eva Grundschober,
- Karin Bauer,
- Mareike Roth,
- Anna Skucha,
- Yao Liu,
- John M. Hatcher,
- Yanke Liang,
- Nicholas P. Kwiatkowski,
- Daniela Fux,
- Andrea Hoelbl-Kovacic,
- Stefan Kubicek,
- Junia V. Melo,
- Peter Valent,
- Thomas Weichhart,
- Florian Grebien,
- Johannes Zuber,
- Nathanael S. Gray,
- Veronika Sexl
Affiliations
- Ingeborg Menzl
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Tinghu Zhang
- Department of Cancer Biology, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
- Angelika Berger-Becvar
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Reinhard Grausenburger
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Gerwin Heller
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Michaela Prchal-Murphy
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Leo Edlinger
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Vanessa M. Knab
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Iris Z. Uras
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Eva Grundschober
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Karin Bauer
- Division of Hematology and Hemostaseology, Department of Internal Medicine I, Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna
- Mareike Roth
- Research Institute of Molecular Pathology
- Anna Skucha
- Ludwig Boltzmann Institute for Cancer Research
- Yao Liu
- Department of Cancer Biology, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
- John M. Hatcher
- Department of Cancer Biology, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
- Yanke Liang
- Department of Cancer Biology, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
- Nicholas P. Kwiatkowski
- Department of Cancer Biology, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
- Daniela Fux
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Andrea Hoelbl-Kovacic
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- Stefan Kubicek
- Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Junia V. Melo
- Faculty of Health and Medical Sciences, University of Adelaide
- Peter Valent
- Division of Hematology and Hemostaseology, Department of Internal Medicine I, Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna
- Thomas Weichhart
- Center of Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna
- Florian Grebien
- Ludwig Boltzmann Institute for Cancer Research
- Johannes Zuber
- Research Institute of Molecular Pathology
- Nathanael S. Gray
- Department of Cancer Biology, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
- Veronika Sexl
- Institute of Pharmacology and Toxicology, University of Veterinary Medicine
- DOI
- https://doi.org/10.1038/s41467-019-12656-x
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
Cyclin-dependent kinases are deregulated in blood cancers. Here, the authors show that CDK8, independent of its kinase activity, regulates mTOR signalling for the maintenance of BCR-ABL1+ leukemia, and that the dual inhibition of CDK8 and mTOR signalling induces apoptosis in these cells.