The functional inactivation of tumor suppressor genes (anti-oncogenes) plays an important role in tumorigenesis. The inactivation of these genes is postulated to result in loss of responsiveness to growth inhibitory signals, allowing uncontrolled growth. One tumor-suppressor gene, the retinoblastoma (Rb) gene is thought to regulate cell growth by repressing the transcription of growth stimulatory genes, such as c-fos, and stimulating the transcription of growth inhibitory genes, such as TGFbeta via cis-acting DNA sequences called retinoblastoma control elements (RCE). Recent experimental evidence suggests that Rb functions to regulate transcription by forming inactive complexes with transcription factors. To enhance our understanding of Rb function, we have sought to identify an Rb-like pathway in yeast. Preliminary work has identified an RCE-specific binding protein of 200 kd (p2OO) from the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. This result suggests that a conserved transcriptional regulatory network may exist in both yeast and mammalian cells. Assuming that the yeast RCE-binding protein is structurally as well as functionally homologous to a mammalian RCE-binding factor, we propose to use yeast to facilitate the cloning of mammalian RCE-binding factors, as well as determine if a transcriptional regulatory pathway controlled by an Rb-like protein exists in yeast.
| Cuevo, R S; Garrett, S; Horowitz, J M (1997) Detection and functional characterization of p180, a novel cell cycle regulated yeast transcription factor that binds retinoblastoma control elements. J Biol Chem 272:3813-22 |
