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Targeting APL Fusion Proteins by Peptide Interference

  • A. Melnick
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 313)

Abstract

A significant barrier to experimental therapeutics is the ability to identify and specifically target oncogenic proteins involved in the molecular pathogenesis of disease. In acute promyelocytic leukemia (APL), aberrant transcription factors and their associated machinery play a central role in mediating the malignant phenotype. The mechanism of action of APL chimeric fusion proteins involves their ability to either self-associate or interact with different partner proteins. Thus, targeting protein-protein interactions could have a significant impact in blocking the activity of APL oncoproteins. As therapeutic targets, the interface between interacting proteins may not always be amenable to highly specific small molecule blockade. In contrast, peptides are well-suited to this purpose and can be reliably delivered when fused to cell-permeable peptide domains. Therapeutic peptides can be designed to directly target APL fusion proteins, their downstream effectors, or other potentially synergistic oncogenic mechanisms of importance in APL blasts. In addition to serving as potential therapeutic agents, such reagents could serve as powerful reagents to dissect the molecular pathogenesis of APL.

Keywords

Arsenic Trioxide Protein Transduction Domain Therapeutic Peptide SMRT Corepressor Acute Promyelocytic Leukemia Blast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • A. Melnick
    • 1
  1. 1.Department of Developmental and Molecular Biology and Medical OncologyAlbert Einstein College of MedicineBronxUSA

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