Two-step model for GAL induction. Gal4p is bound to the upstream activating sequence of galactose-inducible genes in a complex with Gal80p in the absence of galactose (35, 36), causing no transcription (uninduced state). Galactose, when added to the medium, binds Gal3p in the presence of ATP resulting in a stable complex formation with Gal80p. Binding of Gal3p to Gal80p in turn causes a structural alteration of Gal80p/Gal4p complex, which makes the activation domain (AD) of Gal4p accessible to the transcription preinitiation complex, and thereby activates the transcription (establishment of induction). Gal4p, once engaged in transcriptional activation, is phosphorylated at a critical site (ref. 34, see text). The properly phosphorylated Gal4p is kept functioning as long as the critical site is phosphorylated (maintenance of induction). For simplicity, the model is tentatively drawn based on the allosteric model (35). This does not necessarily mean that we presently have evidence to rule out the dissociation model.