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Discovery of relationship between proteins may impact development of cancer therapies
Date:4/19/2011

By identifying a surprising association of two intracellular proteins, University of Iowa researchers have laid the groundwork for the development of new therapies to treat B cell lymphomas and autoimmune disease.

The researchers studied mouse B cells expressing the viral protein Latent Membrane Protein 1 (LMP1), which has been implicated in several types of cancer because of its role in the proliferation and survival of Epstein-Barr virus infected B cells. They discovered that LMP1 needs the cellular protein Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) to promote its B cell activation signaling pathways.

The study, published recently in the Journal of Biological Chemistry, also shows that LMP1 and CD40 a normal activating receptor of B cells both use TRAF6 as a key signaling protein, but in different ways. LMP1 mimics CD40 in delivering activation signals to B cells, but LMP1's signals are amplified and sustained, resulting in B cell hyper-activation.

B cells are a type of white blood cell. They normally mature into plasma cells that produce proteins called antibodies necessary to fight off infections. But in the process of modifying antibody genes, mistakes can cause mutations. With an accumulation of such mutations, B cells can become cancerous, which is why B cell malignancies are relatively common.

"We found that TRAF6 is essential for LMP1 functions, and that it interacts with LMP1 in a way that is distinct from the way in which TRAF6 interacts with CD40," said lead author Kelly Arcipowski, a Ph.D. candidate in the UI Molecular and Cellular Biology Interdisciplinary Graduate Program. "Thus, it might be possible to target LMP1 signaling without disrupting normal immune function. This information is valuable to the development of new therapies to target LMP1-mediated pathogenesis, including B cell lymphomas and autoimmune disease."

B-cell lymphomas include Hodgkin's lymphomas and most no
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa Health Care
Source:Eurekalert

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