In cells of Saccharomyces cerevisiae, using ammonia as a source of nitrogen, Gln3p is sequestered in the cytoplasm by Ure2p but enters the nucleus when the cells are shifted to a nonpreferred source of nitrogen such as proline. The interpretation of recently published observations provides evidence for the view that Ure2p is the sensor for a drop in the intracellular concentration of glutamine, a signal that results in the polyubiquitination of the vesicle responsible for retaining the Gln3p-Ure2p complex in the cytoplasm. As a consequence of the drop in glutamine concentration, Gln3p is able to enter the nucleus and to activate the transcription of nitrogen-regulated genes.