Journal article
Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7
IE Wertz, S Kusam, C Lam, T Okamoto, W Sandoval, DJ Anderson, E Helgason, JA Ernst, M Eby, J Liu, LD Belmont, JS Kaminker, KM O'Rourke, K Pujara, PB Kohli, AR Johnson, ML Chiu, JR Lill, PK Jackson, WJ Fairbrother Show all
Nature | NATURE PUBLISHING GROUP | Published : 2011
DOI: 10.1038/nature09779
Abstract
Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, M..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank P. Ekert for FDM cell lines, J. Stinson for sequencing assistance, S. Johnson and C. Santos for assistance with obtaining patient samples, P. Haverty for bioinformatics analysis, C. Grimaldi for cloning assistance, J. Dynek for TaqMan advice, D. French for tumour analysis, C. Quan and J. Tom for peptide synthesis, I. Zilberleyb and the Baculovirus Expression Group for cloning and protein production, S. Charuvu for generating MCL1 point mutants, A. Bruce for graphics assistance, the Genentech Cancer Genome Project Team, Z. Modrusan, R. Soriano and the microarray lab for ovarian tumour data sets, K. Newton for editorial assistance, W. Wei for sharing unpublished results, and A. Eldridge, D. Kirkpatrick, D. Vucic, E. Varfolomeev, T. Goncharov, A. Cochran, O. Huang, A. Huang, Y. Pereg, A. Loktev, D. Phillips, J. Wu, M. van Delft, D. Eaton, E. Shaulian, T. Hunter, S. Cory, J. Adams, A. Strasser, R. Deshaies and G. Evan for discussions. Work in the Huang laboratory is supported by the National Health and Medical Research Council (program grant #461221, IRIISS grant #361646 and a fellowship to D.C.S.H.), the Leukemia and Lymphoma Society (SCOR 7413), the National Institutes of Health (grants CA043540 and CA80188), the Australian Cancer Research Foundation, and an Australian Research Council Australian Postdoctoral fellowship to T.O. We apologize to our colleagues whose primary work could not be cited owing to space constraints.