Molecular Systems Biology | The Seven Stones

[Research highlight] NF-kappaB signaling goes digital

In a report published this week at Nature, Tay et al. reveal that populations of mouse 3T3 cells exposed to TNF-α show a digital NF-κB response, where increasing TNF-α concentrations lead to a higher proportion of cells with nuclear localized NF-κB — an effect that depends, in part, on pre-existing heterogeneity within the cell population. These results provide another compelling example of the way that studies using single cell measurements are transforming our understanding of cellular signaling mechanisms. Interestingly, these results seem to contrast with another recent single-cell-based study of NF-κB dynamics (Giorgetti et al. 2010), which observed a relatively uniform population-level NF-κB response to TNF-α in human HCT116 cells, indicating that there is still much to learn about the dynamics of NF-κB signaling.

Giorgetti L, Siggers T, Tiana G, Caprara G, Notarbartolo S, Corona T,

Pasparakis M, Milani P, Bulyk ML, Natoli G (2010) Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs. Mol Cell 37:418-28

Tay S, Hughey JJ, Lee TK, Lipniacki T, Quake SR, Covert MW (2010) Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing. Nature 466:267-71

→ Also, see Cheong et al. for a history of systems biology modeling of NF-κB signaling:

Cheong R, Hoffmann A, Levchenko A (2008) Understanding NF-kappaB signaling via mathematical modeling. Mol Syst Biol 4:192.


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    Mike said:

    T-cell receptor signaling leads to digital NF-kappaB activation:

    Cutting edge: TCR ligation triggers digital activation of NF-kappaB. J Immunol. 2010 Oct 15;185(8):4520-4. Epub 2010 Sep 20.