Microtubule-damaging drugs triggered bcl2 phosphorylation-requirement of phosphorylation on both serine-70 and serine-87 residues of bcl2 protein.
Specifically anti-microtubule agents such as taxol, vincristine, vinblastine and dolastatin can trigger Bcl2 phosphorylation at G2-M phase of the cell cycle in malignant cells derived from a variety of human cancers. In this study, the status of Bcl2 phosphorylation was investigated in response to more antimicrotubule agents such as colchicine, colcemid or podophyllotoxin. Although these agents are not currently used for cancer therapy, they were able to trigger Bcl2 phosphorylation with simultaneous apoptosis in cancer cells. Previously, by using extensive site-directed mutagenesis studies we determined that mutation of serine-70 to alanine could not completely abrogate taxol induced Bcl2 phosphorylation. Studies reported here clearly indicate that serine-87 residue along with serine-70 of Bcl2 protein are necessary for microtubule damaging drug induced phosphorylation.
Basu
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Rammelkamp Center for Education and Research, Department of Pharmacology, Ireland Cancer Center, MetroHealth/Case Western Reserve University, Cleveland, OH 44109-1998, USA.
Haldar
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S
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones; D001665:Binding Sites / Q000235:genetics; D003078:Colchicine / Q000494:pharmacology; D003703:Demecolcine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006074:Gout Suppressants / Q000494:pharmacology; D006801:Humans; D047029:Lactams, Macrocyclic; D008870:Microtubules / Q000187:drug effects*; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D017239:Paclitaxel / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011034:Podophyllotoxin / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D047029:Lactams, Macrocyclic; D019253:Proto-Oncogene Proteins c-bcl-2; D011809:Quinones; D012694:Serine; D019908:Proto-Oncogene Proteins c-raf; D011034:Podophyllotoxin; D017239:Paclitaxel; D003078:Colchicine; D003703:Demecolcine; C001277:geldanamycin