title: Phospho-Bcl-xL(Ser62) influences spindle assembly and chromosome segregation during mitosis.
abstract: Functional analysis of a series of phosphorylation mutants reveals that Bcl-xL(Ser62Ala) influences cell entry into anaphase and mitotic exit in taxol-exposed cells compared with cells expressing wild-type Bcl-xL or a series of other phosphorylation mutants, an effect that appears to be independent of its anti-apoptotic activity. During normal mitosis progression, Bcl-xL(Ser62) is strongly phosphorylated by PLK1 and MAPK14/SAPKp38α at the prometaphase, metaphase, and the anaphase boundaries, while it is de-phosphorylated at telophase and cytokinesis. Phospho-Bcl-xL(Ser62) localizes in centrosomes with γ-tubulin and in the mitotic cytosol with some spindle-assembly checkpoint signaling components, including PLK1, BubR1, and Mad2. In taxol- and nocodazole-exposed cells, phospho-Bcl-xL(Ser62) also binds to Cdc20- Mad2-, BubR1-, and Bub3-bound complexes, while Bcl-xL(Ser62Ala) does not. Silencing Bcl-xL expression and expressing the phosphorylation mutant Bcl-xL(Ser62Ala) lead to an increased number of cells harboring mitotic spindle defects including multipolar spindle, chromosome lagging and bridging, aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h. Together, the data indicate that during mitosis, Bcl-xL(Ser62) phosphorylation impacts on spindle assembly and chromosome segregation, influencing chromosome stability. Observations of mitotic cells harboring aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h were also made with cells expressing the phosphorylation mutant Bcl-xL(Ser49Ala) and dual mutant Bcl-xL(Ser49/62Ala).
authors.affiliation: Centre de recherche; Centre hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal; Montréal, Québec, Canada.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Centre de recherche; Centre hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal; Montréal, Québec, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Beauchemin
authors.affiliation: Centre de recherche; Centre hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal; Montréal, Québec, Canada; Département de médecine; Université de Montréal; Montréal, Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Bertrand
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D050257:Tubulin Modulators / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D048308:Mitogen-Activated Protein Kinase 14; D015739:Nocodazole; D017239:Paclitaxel; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012694:Serine; D050257:Tubulin Modulators; D051020:bcl-X Protein; D000097869:Polo-Like Kinase 1; C494811:BCL2L1 protein, human
keywords: Bcl-xL; MAPK14/SAPKp38α; PLK1; chromosome instability; chromosome segregation; mitosis; spindle-assembly checkpoint