title: Polo-like kinase 1 phosphorylates and regulates Bcl-x(L) during pironetin-induced apoptosis.
abstract: Bcl-x(L), an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although Bcl-x(L) is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a Bcl-x(L) kinase. Same location of Bcl-x(L) and Plk1 was revealed by immunocytochemical analyses at M-phase in situ. Plk1 phosphorylates Bcl-x(L) in vitro, and we identified Plk1 phosphorylation sites in Bcl-x(L). When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the Bcl-x(L) mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of Bcl-x(L) phosphorylation and controls the anti-apoptotic activity of Bcl-x(L) during pironetin-induced apoptosis.
authors.affiliation: Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Simizu
authors.forename: M
authors.initials: M
authors.lastname: Muroi
authors.forename: S
authors.initials: S
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Kawatani
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Osada
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D000409:Alanine; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011753:Pyrones; D012694:Serine; D051020:bcl-X Protein; D000097869:Polo-Like Kinase 1; C088446:pironetin