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Penn study finds pro-death proteins required to regulate healthy immune function

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine have found that proteins known to promote cell death are also necessary for the maturation and proliferation of immune cells. Activation of T-cell receptors on the surface of lymphocytes by foreign antigens initiate a calcium-mediated signaling pathway that ends in cell differentiation and growth. The Penn scientists discovered that in the cells that lack the pro-death proteins Bax and Bak, calcium signaling is disrupted and energy production is reduced. Restoration of Bax corrects the signaling problems, increases energy production, and stimulates cell division.

The results, published online in the journal Immunity, bolster the teams hypothesis that metabolic cell activity directly controls life and death decisions in cells. This issue also includes a related commentary by the studys lead author, Russell Jones, PhD, and senior author Craig B. Thompson, MD.

It is well known that cells that lack Bax (Bcl-2-associated X protein) and Bak (Bcl-2-antagonist/killer) continue living under conditions that would cause normal cells to undergo programmed cell death or apoptosis. What is less well understood, is why lymphocytes missing these key proteins are unable to trigger a strong immune response and do not proliferate as normal in response to stimulation.

We simply say they are the same thing, says Thompson, Director of the Abramson Cancer Center and Chairman and Professor of Cancer Biology and Medicine. The molecular basis of both findings is based on how Bax and Bak work on intracellular membranes.

Specifically, the team found that when the T-cell receptor was stimulated on mutant cells lacking both proteins, proliferation was severely reduced relative to normal cells. Closer investigation showed that the amount and rate of calcium release from intracellular stores was altered in the mutant cells.

The inadequate calcium signals were unable
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
10-Aug-2007


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