DETECTION AND FUNCTIONAL-CHARACTERIZATION OF P180, A NOVEL CELL-CYCLE-REGULATED YEAST TRANSCRIPTION FACTOR THAT BINDS RETINOBLASTOMA CONTROL ELEMENTS

In recent years it has become apparent that the cellular machinery gov erning cell cycle progression and transcription control are often homo logous in yeast and mammalian cells, We and others have previously sho wn that the SP family of mammalian transcription factors regulates the transcription of a number of genes whose activities are governed by t he product of the retinoblastoma (Rb) susceptibility gene, including c -FOS, c-MYC, TGF beta-1, IGF-II, and c-JUN, To determine whether a sim ilar pathway of transcriptional regulation may function in yeast, we e xplored the possibility that transcription factors with nucleotide-bin ding specificities akin to those of the SP family are expressed in Sac charomyces cerevisiae and Schizosaccharomyces pombe, Here we report th e detection of novel yeast proteins (S. cerevisiae, p180; S. pombe, p2 00) that specifically bind Rb-regulated promoter elements in vitro dep endent on nucleotides that are also required for binding and trans-act ivation by SP family members in vivo. Our results indicate that the S. cerevisiae retinoblastoma control element-binding activity 1) require s zinc for association with DNA; 2) does not bind to SCB, MCB, or E2F sites in vitro; 3) is cell cycle-regulated in a SWI6-independent fashi on; and 4) maximally stimulates retinoblastoma control element-mediate d transcription in early- to mid-S phase. Taken together, these data s uggest that p180 may regulate the transcription of a subset of yeast g enes whose expression is coincident with the onset and/or progression of DNA replication.