Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae

The yeast transcription factor Ace2p regulates expression of the chitinase gene CTS1 in a cell cycle-dependent manner. Nuclear localisation of Ace2p i s restricted to late M and early G1 phases of the mitotic cell cycle. We sh ow here that this nuclear localisation is directly associated with regulati on of CTS1 expression. Using a version of Ace2p tagged with a c-myc epitope , we show that the protein is excluded from the nucleus of cells during mos t phases of the mitotic cell cycle. A mutant derivative in which one threon ine and two serine residues, which are candidate phosphorylation sites, wer e replaced by alanine (to mimic constitutive dephosphorylation) is localise d in the nucleus throughout the cell cycle. The mechanism of localisation o f Ace2p therefore involves regulation of its phosphorylation state, and clo sely resembles that used by the homologous transcription factor Swi5p. The wild-type Ace2 protein associates with Cdc28p in vivo, suggesting this may be the kinase that mediates the phosphorylation event. The stability of the protein is greatly reduced in a mutant that is constitutively localised to the nucleus, but is restored in a deletion derivative which remains in the cytoplasm. Ace2p is therefore controlled throughout the cell cycle at thre e levels: transcription, nuclear localisation, and proteolysis.