title: Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints.
abstract: Functional analysis of a Bcl-xL phosphorylation mutant series has revealed that cells expressing Bcl-xL(Ser49Ala) mutant are less stable at G2 checkpoint after DNA damage and enter cytokinesis more slowly after microtubule poisoning, than cells expressing wild-type Bcl-xL. These effects of Bcl-xL(Ser49Ala) mutant seem to be separable from Bcl-xL function in apoptosis. Bcl-xL(Ser49) phosphorylation is cell cycle-dependent. In synchronized cells, phospho-Bcl-xL(Ser49) appears during the S phase and G2, whereas it disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during telophase and cytokinesis. During DNA damage-induced G2 arrest, an important pool of phospho-Bcl-xL(Ser49) accumulates in centrosomes which act as essential decision centers for progression from G2 to mitosis. During telophase/cytokinesis, phospho-Bcl-xL(Ser49) is found with dynein motor protein. In a series of in vitro kinase assays, specific small interfering RNA and pharmacological inhibition experiments, polo kinase 3 (PLK3) was implicated in Bcl-xL(Ser49) phosphorylation. These data indicate that, during G2 checkpoint, phospho-Bcl-xL(Ser49) is another downstream target of PLK3, acting to stabilize G2 arrest. Bcl-xL phosphorylation at Ser49 also correlates with essential PLK3 activity and function, enabling cytokinesis and mitotic exit.
authors.affiliation: Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM), Hôpital Notre-Dame and Institut du cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Wang
authors.forename: Myriam
authors.initials: M
authors.lastname: Beauchemin
authors.forename: Richard
authors.initials: R
authors.lastname: Bertrand
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D048750:Cell Nucleus Division; D056744:Cyclin B1 / Q000378:metabolism; D048749:Cytokinesis; D004249:DNA Damage; D059565:G2 Phase Cell Cycle Checkpoints; D006657:Histones / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein / Q000378:metabolism*; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012694:Serine; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D000097869:Polo-Like Kinase 1; C494811:BCL2L1 protein, human; C534699:CCNB1 protein, human; C486256:PLK3 protein, human; D000097868:Polo-like Kinases