The kinase knows

new report shows that a eukaryotic transcription factor is directly activated by a metabolite of the pathway it controls. Although this idea has been proposed for several regulatory systems, Christopher Sellick and Richard Reece (University of Manchester, UK) are the first to demonstrate direct binding to and activation of a eukaryotic transcription factor by a small molecule metabolite. The interaction controls the activity of yeast Put3p, an activator of PUT1 and PUT2 transcription. Put1p and Put2p convert proline into glutamate— a high quality source of nitrogen. Put3p binds upstream of the enzymes’ transcription start sites whether or not proline is available, but Sellick and Reece show that waste is avoided by limiting activation to proline-rich conditions. In vitro, Put3p alone was inactive, but transcriptional activation required only the addition of proline. The direct binding of proline to Put3p was weak, probably so the pathway is turned on only when proline is abundant. When preferred nitrogen sources such as glutamine are present, Put3p is inactive even in the presence of proline, suggesting that other mechanisms ensures that proline is converted only when alternative sources are not available.