Originally identified as a Suppressor gene for FLocculation, SFL1 encodes a 766-amino acid transcriptional repressor of flocculation-related genes (1, 2). SFL1 is required for normal cell-surface assembly in vegetative growth (1), and deletion enhances pseudohyphal and invasive growth (2).

Sfl1p contains two domains homologous to Myc oncoproteins and the yeast heat shock transcription factor Hsf1p (1). The Myc homologous region in Sfl1p overlaps with conserved regions in other eukaryotic proteins including mammalian MyoD1 and immunoglobulin enhancer-binding proteins, as well as Drosophila achaete-scute, twist and daughterless gene products. The N-terminal region of Sfl1p shows homology to the DNA-binding domain of Hsf1p (1).

Two-hybrid analysis has indicated that Sfl1p interacts specifically with Tpk2p, the catalytic subunit of protein kinase A, which negatively regulates Sfl1p function (2, 4, 3). Phosphorylation by protein kinase A relieves Sfl1p-mediated repression by prohibiting dimerization and DNA-binding by Sfl1p (4), and a tpk2Delta mutation increases the levels of Sfl1p protein associated with specific promoter elements (3).

Yeast two-hybrid and GST chromatography interaction experiments determined that Sfl1p interacts directly with Cyc8p, a component of the general corepressor Cyc8p-Tup1p that inhibits the transcription of many diversely regulated genes (3). Electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrate that Sfl1p is present at the promoters of Cyc8p-Tup1p-repressible genes, and repression data suggest that Sfl1p inhibits transcription by recruiting Cyc8p-Tup1p via a specific domain in the Sfl1p protein (3). Co-immunoprecipitation experiments link Sfl1p to Ssn2p, Ssn8p, Sin4p and Rox3p, suggesting that Sfl1p may interact with Srb/mediator proteins to inhibit transcription by the RNA polymerase II holoenzyme (6). Sin4p and Ssn3p, components of specific RNA polymerase II subcomplexes required for Cyc8p-Tup1p repression activity, are required for Sfl1p repression function, indicating a possible mechanism for Sfl1p-mediated repression via Cyc8p-Tup1p and specific subunits of the RNA polymerase II holoenzyme (3). Taken together with previous data, these observations suggest a link between cAMP signaling and Cyc8p-Tup1p-mediated transcriptional repression (3).

Last updated: 2005-05-03