Activation of the transcription factor NFAT1:: concerted or modular regulation?

The transcription factor NFAT1 is activated through dephosphorylation of multiple serine residues, contained within the SRR1 and SP motifs. The phosphorylation status of these motifs regulates the subcellular localisation of NFAT1 via a conformational switch. Here, we discuss two molecular mechanisms for NFAT1 activation that resemble network-oriented approaches. In the modular mechanism, import and export are regulated separately by the SRR1 and SP motifs, respectively, whereas in the concerted model all residues jointly control both processes. Using simulations of a computational model, we show that both mechanisms may be compatible with recent experimental data on the import and export kinetics of NFAT1. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.