The Bcl10/Malt1 signaling pathway as a drug target in lymphoma.
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-kappaB 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.
Jost
P
P
Third Medical Department, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany.
Peschel
C
C
Ruland
J
J
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000074018:B-Cell CLL-Lymphoma 10 Protein; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D061945:Caspase Inhibitors; D009363:Neoplasm Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein