Bax345/BLyS: a novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin.

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.

• Authors: Mi-Ae Lyu, Lawrence H Cheung, Walter N Hittelman, Yuying Liu, John W Marks, Min-Jeong Cho, Michael G Rosenblum
• Journal: Cancer letters (Cancer Lett) Vol. 322 Issue 2 Pg. 159-68 (Sep 28 2012) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22388102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• B-Cell Activating Factor
• Bax345-BLyS fusion protein, human
• Inhibitor of Apoptosis Proteins
• Recombinant Fusion Proteins
• bcl-2-Associated X Protein
• Cytochromes c

Topics

• Apoptosis (drug effects, genetics)
• B-Cell Activating Factor (genetics)
• Cell Cycle Checkpoints (drug effects, genetics)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Gene Order
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• Inhibitory Concentration 50
• Lymphoma, B-Cell (drug therapy, metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Protein Binding
• Protein Transport
• Recombinant Fusion Proteins (genetics, metabolism, toxicity)
• bcl-2-Associated X Protein (genetics)