title: Phosphorylation of BAD at Ser-128 during mitosis and paclitaxel-induced apoptosis.
abstract: Phosphorylation of BCL-2 family member BAD at different residues triggers different physiological effects, either inhibiting or promoting apoptosis. The recently identified phosphorylation site at Ser-128 enhances the apoptotic activity of BAD. We here show that BAD becomes phosphorylated at Ser-128 in the mitotic phase of the cell cycle in NIH3T3 cells. We also show that BAD-S128 is phosphorylated in taxol-treated mouse fibroblasts and MDA-MB-231 human breast cancer cells. However, expression of a phosphorylation-defective dominant negative BAD mutant did not block taxol-induced apoptosis. These data support the view that the phosphorylation of BAD Serine 128 exerts cell-specific effects on apoptosis. Whereas the BAD Serine 128 phosphorylation induces apoptosis in neuronal cells, it does not appear to promote apoptosis in proliferating non-neural cells during mitosis or upon exposure to the antineoplastic agent taxol.
authors.affiliation: Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Berndtsson
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Konishi
authors.forename: Azad
authors.initials: A
authors.lastname: Bonni
authors.forename: Maria
authors.initials: M
authors.lastname: Hägg
authors.forename: Maria
authors.initials: M
authors.lastname: Shoshan
authors.forename: Stig
authors.initials: S
authors.lastname: Linder
authors.forename: Aleksandra Mandic
authors.initials: AM
authors.lastname: Havelka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein
chemical_list: C494819:BAD protein, human; C494820:Bad protein, mouse; D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D010768:Phosphoserine; D017239:Paclitaxel