Abstract
Apoptosis or programmed cell death is essential in the process of controlling lymphocyte growth and selection. We identified proteins that are involved in anti-IgM antibody-mediated apoptosis using a subclone of the human Burkitt lymphoma cell line BL60. Apoptosis-associated proteins were detected by high resolution two-dimensional gel electrophoresis on a micropreparative scale. Comparison of the high resolution two-dimensional gel electrophoresis protein patterns from apoptotic and non-apoptotic cells showed differences in approximately 80 spots including protein modifications. Analysis of the predominantly altered proteins was performed by internal Edman microsequencing and/or by peptide mass fingerprinting using matrix-assisted laser desorption/ionization mass spectrometry. Analysis was significantly improved by using new micropreparative high resolution two-dimensional gels employing high protein concentrations. The following 12 apoptosis-associated proteins were identified: heterogeneous nuclear ribonucleoprotein (hnRNP) A1, hnRNP C1/C2, FUSE-binding protein, dUTPase, lymphocyte-specific protein LSP1, UV excision repair protein RAD23 homologue B (HHR23B), 60 S acidic ribosomal protein P0 (L10E), heterochromatin protein 1 homologue alpha (HP1alpha), nucleolin, lamin, neutral calponin, and actin. Fragmentation of actin, hnRNP A1, hnRNP C1/C2, 60 S acidic ribosomal protein P0, lamin, and nucleolin could be inhibited by benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl ketone, a selective irreversible inhibitor of CPP32 (caspase 3).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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Burkitt Lymphoma / metabolism*
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Calcium-Binding Proteins / metabolism
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Caspase 3
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Caspase Inhibitors
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Caspases / metabolism*
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Chromobox Protein Homolog 5
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Chromosomal Proteins, Non-Histone / metabolism
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DNA Repair Enzymes
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DNA-Binding Proteins / metabolism
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Electrophoresis, Gel, Two-Dimensional
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Heterogeneous Nuclear Ribonucleoprotein A1
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B*
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Heterogeneous-Nuclear Ribonucleoprotein Group C*
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Heterogeneous-Nuclear Ribonucleoproteins
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Humans
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Immunoglobulin M
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Immunologic Capping
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Immunomagnetic Separation
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Lamins
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Microfilament Proteins
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / metabolism
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Nucleolin
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Oligopeptides / pharmacology
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Phosphoproteins / metabolism
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Pyrophosphatases / metabolism
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RNA, Heterogeneous Nuclear
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RNA-Binding Proteins / metabolism
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Receptors, Antigen, B-Cell
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Ribonucleoproteins / metabolism*
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Ribosomal Proteins / metabolism
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Tumor Cells, Cultured
Substances
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C1 HNRNP
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CBX5 protein, human
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Calcium-Binding Proteins
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Caspase Inhibitors
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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HNRNPC protein, human
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Heterogeneous Nuclear Ribonucleoprotein A1
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B
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Heterogeneous-Nuclear Ribonucleoprotein Group C
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Heterogeneous-Nuclear Ribonucleoproteins
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Immunoglobulin M
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LSP1 protein, human
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Lamins
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Microfilament Proteins
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Neoplasm Proteins
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Nuclear Proteins
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Oligopeptides
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Phosphoproteins
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RAD23B protein, human
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RNA, Heterogeneous Nuclear
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RNA-Binding Proteins
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Receptors, Antigen, B-Cell
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Ribonucleoproteins
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Ribosomal Proteins
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benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
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hnRNPA1 protein, human
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ribosomal protein P0
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Chromobox Protein Homolog 5
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RAD23A protein, human
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CASP3 protein, human
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Caspase 3
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Caspases
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Pyrophosphatases
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dUTP pyrophosphatase
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DNA Repair Enzymes