title: Inactivation of Bcl-2 by phosphorylation.
abstract: The antiapoptosis potential of Bcl-2 protein is well established, but the mechanism of Bcl-2 action is still poorly understood. Using the phosphatase inhibitor okadaic acid or the chemotherapeutic drug taxol, we found that Bcl-2 was phosphorylated in lymphoid cells. Phospho amino acid analysis revealed that Bcl-2 was phosphorylated on serine. Under similar conditions, okadaic acid or taxol treatment led to the induction of apoptosis in these cells. Thus, phosphorylation of Bcl-2 seems to inhibit its ability to interfere with apoptosis. In addition, phosphorylated Bcl-2 can no longer prevent lipid peroxidation as required to protect cells from apoptosis.
authors.affiliation: Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: S
authors.initials: S
authors.lastname: Haldar
authors.forename: N
authors.initials: N
authors.lastname: Jena
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D015870:Gene Expression; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008214:Lymphocytes; D019319:Okadaic Acid; D017239:Paclitaxel / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection
chemical_list: D004988:Ethers, Cyclic; D005231:Fatty Acids, Unsaturated; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases; D017239:Paclitaxel; C013641:parinaric acid