Abstract
We generated a fusion protein Bax(345)/BLyS containing the truncated form of Bax (Bax(345)) at the N-terminus followed by a 218 linker to the B lymphocyte stimulator (BLyS). Bax(345)/BLyS was cytotoxic to a panel of diffuse large B cell lymphoma and mantle cell lymphoma lines expressing the BLyS receptors. Specific delivery of Bax(345)/BLyS to malignant B cells drove cells into apoptosis by mitochondrial dysfunction and treatment of cells with Bax(345)/BLyS induced down-regulation of Mcl-1, X-IAP, and survivin. Bax(345)/BLyS represents a new class of targeted therapeutic agents with a unique mechanism of action and may have therapeutic potential for malignant B cells.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / genetics
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B-Cell Activating Factor / genetics*
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / genetics
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Cell Line, Tumor
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Cytochromes c / metabolism
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Gene Order
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Humans
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Inhibitor of Apoptosis Proteins / metabolism
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Inhibitory Concentration 50
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Lymphoma, B-Cell / drug therapy
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Lymphoma, B-Cell / metabolism*
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Membrane Potential, Mitochondrial / drug effects
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Protein Binding
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Protein Transport
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / toxicity*
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bcl-2-Associated X Protein / genetics*
Substances
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B-Cell Activating Factor
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Bax345-BLyS fusion protein, human
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Inhibitor of Apoptosis Proteins
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Recombinant Fusion Proteins
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bcl-2-Associated X Protein
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Cytochromes c