Therapeutic Potential of Furin Inhibition

Therapeutic Potential of Furin Inhibition
An Evaluation Using A Conditional Furin Knockout Mouse Model

Jeroen Declercq, J.W.M. Creemers
ISBN: 9781615045259 | PDF ISBN: 9781615045266
Copyright © 2012 | 30 Pages | Publication Date: 11/01/2012

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The proprotein convertase Furin is a serine endoprotease which cleaves protein precursors carboxyterminal of basic residues in motifs such as Arg-X-X-Arg and Lys/Arg-Arg. Cleavage usually results in activation of the proprotein but can also inactivate or modify the activity. Therefore, it is not surprising that it plays a major role in many physiological processes and pathologies, including cancer. The other proprotein convertases belonging to the same family, PC1/3, PC2, PACE4, PC4, PC5/6, and PC7, cleave at similar cleavage sites and provide partial redundancy. To unravel the specific role of Furin in vivo, knockout mouse models have been generated. Furin null mice die between e10.5 and e11.5 due to severe ventral closure defects and the failure of the heart tube to fuse and undergo looping morphogenesis. Therefore, a conditional Furin knockout mouse was generated to investigate the role of Furin in specific organs, such as pancreas, liver, T-cells, endothelial cells, and salivary glands, resulting in a severe or mild phenotype depending on the organ investigated. Partial or complete ablation of the Fur gene in salivary gland tumors significantly delayed tumorigenesis in mice. Therefore, Furin inhibition might be considered as a possible therapeutic strategy to treat certain pathologies, such as cancer.

Table of Contents

Background Introduction
Generation of a Conditional Furin Ko Mouse
Furin and Cancer
Furin Inhibitors
Conclusion
References

About the Author(s)

Jeroen Declercq, Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, University of Leuven, Belgium

J.W.M. Creemers, Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, University of Leuven, Belgium

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