The Bcl10 / Malt1 Signaling Pathway as a Drug Target in Lymphoma

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Abstract:

The development of lymphomas and leukemias is frequently caused by chromosomal translocations that deregulate cellular pathways of differentiation, proliferation or survival. The molecules that are involved in these aberrations provide rational targets for selective drug therapies. Recently, several disease specific translocations have been identified in human MALT lymphoma. These aberrations either upregulate the expression of BCL10 or MALT1 or induce the formation of API2-MALT1 fusion proteins. Genetic and biochemical experiments identified BCL10 and MALT1 as central components of an oligomerization - ubiquitinylation - phosphorylation cascade that activates the transcription factor NF-κB in response to antigen receptor ligation. Deregulation of the signaling cascade is directly associated with antigen independent MALT lymphoma growth. Here we provide an overview of the physiological and pathological functions of BCL10 / MALT1 signal transduction and discuss the potential of this pathway as a drug target.





Keywords: API2-MALT1; Bcl10; Lymphoma; Malt1; NF-κB; antigen receptor; chromosomal translocation; fusion protein

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/138945006778559256

Affiliations: Third Medical Department,Technical University of Munich, Klinikum rechts der Isar, Ismaninger Str.22, 81675 Munich, Germany.

Publication date: October 1, 2006

More about this publication?
  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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