Predicting Responses on the Death Pathway

Science's STKE  13 Dec 2005:
Vol. 2005, Issue 314, pp. tw448
DOI: 10.1126/stke.3142005tw448

Multiple signaling pathways can influence whether a cell commits to the cell death program known as apoptosis. For many years, it has been possible to categorize signals as contributing to the "gas" or to the "brakes." However, predicting the biological outcome of multiple signals that apply some gas here and a stomp on the brakes there has remained a challenge. Janes et al. applied a systems–level approach to this problem and created a model to analyze coupling between almost 8000 measurements of signaling parameters in cultured cells with about 1500 measures of the various stages of apoptosis in cells treated with various combinations of cytokines. The model allows the cellular apoptotic response to be correctly predicted under a variety of conditions.

K. A. Janes, J. G. Albeck, S. Gaudet, P. K. Sorger, D. A. Lauffenburger, M. B. Yaffe, A systems model of signaling identifies a molecular basis set for cytokine–induced apoptosis. Science 310, 1646–1653 (2005). [Abstract] [Full Text]