Editors' ChoiceCell Biology

Regulated Responses to Irregular Signals

Sci. Signal.  14 Apr 2009:
Vol. 2, Issue 66, pp. ec127
DOI: 10.1126/scisignal.266ec127

Experiments on the effects of hormones or cytokines often compare responses of cells incubated in the presence or absence of the activating compound. But in vivo, cells experience variations in the amount of stimulus that may be irregular or pulsatile. Ashall et al. explored the response of the transcription factor NF-κB (a major mediator of transcriptional responses in immune function) to short pulses of exposure to the cytokine tumor necrosis factor–α (TNFα). Oscillations in the movement of the transcription factor into and out of the nucleus could be synchronized by exposure of cells to pulses of TNFα. Furthermore, whether transcription of particular genes was activated or not depended on the frequency of stimulation and consequent timing of NF-κB translocation. Cells in inflammatory tissues may experience similar changes in stimulation by TNFα, and therefore respond in distinct ways, depending on the timing of the signals received in the cells.

L. Ashall, C. A. Horton, D. E. Nelson, P. Paszek, C. V. Harper, K. Sillitoe, S. Ryan, D. G. Spiller, J. F. Unitt, D. S. Broomhead, D. B. Kell, D. A. Rand, V. Sée, M. R. H. White, Pulsatile stimulation determines timing and specificity of NF-κB–dependent transcription. Science 324, 242–246 (2009). [Abstract] [Full Text]