Editors' ChoiceCell Biology

Mapping Out Redundancy

Sci. Signal.  21 Oct 2008:
Vol. 1, Issue 42, pp. ec363
DOI: 10.1126/scisignal.142ec363

Living organisms often have compensatory signaling mechanisms that allow the loss of function of a single component to be tolerated, even in important regulatory pathways. This makes such pathways robust to potential challenges but makes the job of unraveling and mapping the pathways more difficult. To work around such buffering or functional redundancy, Bakal et al. systematically tested more than 16,000 RNAi combinations in Drosophila tissue culture cells in order to identify regulators of Drosophila Jun NH2-terminal kinase (JNK). Further analysis with phosphoproteomic data and computational models of kinase specificity was used to establish where the components identified fit in a regulatory network. Similar approaches should help to unravel other critical targets for therapeutic modulation of cell function.

C. Bakal, R. Linding, F. Llense, E. Heffern, E. Martin-Blanco, T. Pawson, N. Perrimon, Phosphorylation networks regulating JNK activity in diverse genetic backgrounds. Science 322, 453-456 (2008). [Abstract] [Full Text]