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Apoptosis of human myeloid leukemia cells induced by an inhibitor of protein phosphatases (okadaic acid) is prevented by Bcl-2 and Bcl-X(L). 1997

A Benito, and A Lerga, and M Silva, and J Leon, and J L Fernandez-Luna
Servicio de Immunologia, Hospital Universitario Marques de Valdecilla, Santander, Spain.

Okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A has been shown to cause mitotic arrest and cell death of HL-60 and K562 cells. HL-60 cells express Bcl-2 and little or no Bcl-X(L), while K562 expresses Bcl-X(L) but not Bcl-2. Since phosphorylation/dephosphorylation reactions have been suggested to be involved in the regulation of Bcl-2, we planned to investigate whether the expression of Bcl-2, Bcl-X(L) and Bax, a protein that antagonizes the antiapoptotic function of Bcl-2, are regulated in myeloid leukemia cell lines (K562, KU812 and HL-60) treated with okadaic acid. Our results indicate that exposure of all three leukemic cell lines to nanomolar concentrations of okadaic acid causes a loss of viability by activation of an apoptotic process accompanied by a marked decrease in the expression of Bcl-2, Bcl-X(L) and Bax at both mRNA and protein level, but not of c-fos, vimentin and epsilon-globin, ruling out a non-specific effect of okadaic acid. Furthermore, constitutive expression of either Bcl-X(L) or Bcl-2 by gene transfer inhibited apoptosis triggered by okadaic acid in K562 cells. Thus, we suggest that protein phosphatases may be involved in maintaining the expression of bcl-2 family genes as part of the survival machinery of the cell.

UI MeSH Term Description Entries
D010749 Phosphoprotein Phosphatases A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) Phosphoprotein Phosphatase,Phosphoprotein Phosphohydrolase,Protein Phosphatase,Protein Phosphatases,Casein Phosphatase,Ecto-Phosphoprotein Phosphatase,Nuclear Protein Phosphatase,Phosphohistone Phosphatase,Phosphoprotein Phosphatase-2C,Phosphoseryl-Protein Phosphatase,Protein Phosphatase C,Protein Phosphatase C-I,Protein Phosphatase C-II,Protein Phosphatase H-II,Protein-Serine-Threonine Phosphatase,Protein-Threonine Phosphatase,Serine-Threonine Phosphatase,Threonine Phosphatase,Ecto Phosphoprotein Phosphatase,Phosphatase C, Protein,Phosphatase C-I, Protein,Phosphatase C-II, Protein,Phosphatase H-II, Protein,Phosphatase, Casein,Phosphatase, Ecto-Phosphoprotein,Phosphatase, Nuclear Protein,Phosphatase, Phosphohistone,Phosphatase, Phosphoprotein,Phosphatase, Phosphoseryl-Protein,Phosphatase, Protein,Phosphatase, Protein-Serine-Threonine,Phosphatase, Protein-Threonine,Phosphatase, Serine-Threonine,Phosphatase, Threonine,Phosphatase-2C, Phosphoprotein,Phosphatases, Phosphoprotein,Phosphatases, Protein,Phosphohydrolase, Phosphoprotein,Phosphoprotein Phosphatase 2C,Phosphoseryl Protein Phosphatase,Protein Phosphatase C I,Protein Phosphatase C II,Protein Phosphatase H II,Protein Phosphatase, Nuclear,Protein Serine Threonine Phosphatase,Protein Threonine Phosphatase,Serine Threonine Phosphatase
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051020 bcl-X Protein A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS and is a regulatory subunit for PROTEIN PHOSPHATASE 1. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL. bcl-XL Protein,bcl-XS Protein,bcl-X(L) Protein,bcl-X(S) Protein,bcl-Xa Protein,bcl-Xalpha Protein,bcl-Xb Protein,bcl-Xbeta Protein,bcl-Xlong Protein,bcl-Xshort Protein,bcl-x(beta) Protein,bcl2-Like 1 Protein,bcl2L1 Protein,bcl X Protein,bcl XL Protein,bcl XS Protein,bcl Xa Protein,bcl Xalpha Protein,bcl Xb Protein,bcl Xbeta Protein,bcl Xlong Protein,bcl Xshort Protein,bcl2 Like 1 Protein
D019253 Proto-Oncogene Proteins c-bcl-2 Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma. bcl-2 Proto-Oncogene Proteins,c-bcl-2 Proteins,B-Cell Leukemia 2 Family Proteins,BCL2 Family Proteins,BCL2 Proteins,B Cell Leukemia 2 Family Proteins,Family Proteins, BCL2,Proteins, BCL2,Proteins, BCL2 Family,Proto Oncogene Proteins c bcl 2,Proto-Oncogene Proteins, bcl-2,bcl 2 Proto Oncogene Proteins,c bcl 2 Proteins,c-bcl-2, Proto-Oncogene Proteins
D019319 Okadaic Acid A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. It is produced by DINOFLAGELLATES and causes diarrhetic SHELLFISH POISONING. Ocadaic Acid

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