title: BCL-W is a regulator of microtubule inhibitor-induced mitotic cell death.
abstract: Microtubule inhibitors including taxanes and vinca alkaloids are among the most widely used anticancer agents. Disrupting the microtubules activates the spindle-assembly checkpoint and traps cells in mitosis. Whether cells subsequently undergo mitotic cell death is an important factor for the effectiveness of the anticancer agents. Given that apoptosis accounts for the majority of mitotic cell death induced by microtubule inhibitors, we performed a systematic study to determine which members of the anti-apoptotic BCL-2 family are involved in determining the duration of mitotic block before cell death or slippage. Depletion of several anti-apoptotic BCL-2-like proteins significantly shortened the time before apoptosis. Among these proteins, BCL-W has not been previously characterized to play a role in mitotic cell death. Although the expression of BCL-W remained constant during mitotic block, it varied significantly between different cell lines. Knockdown of BCL-W with siRNA or disruption of the BCL-W gene with CRISPR-Cas9 speeded up mitotic cell death. Conversely, overexpression of BCL-W delayed mitotic cell death, extending the mitotic block to allow mitotic slippage. Taken together, these results showed that BCL-W contributes to the threshold of anti-apoptotic activity during mitosis.
authors.affiliation: Division of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Division of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.affiliation: Division of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
authors.forename: Randy Y C
authors.initials: RY
authors.lastname: Poon
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D019070:Cell Lineage; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; C491073:BCL2L2 protein, human; D006657:Histones; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D050257:Tubulin Modulators; D049452:Green Fluorescent Proteins; D017239:Paclitaxel
keywords: BCL-2; apoptosis; microtubule; mitosis