and specific aims): Retinoblastoma protein (Rb) function appears to be essential in the differentiation of airway epithelium as well as several other tissues. Conversely, it has recently been suggested that dysregulation of the Rb signal transduction pathway, either through mutation of Rb or aberrant function of another component of the pathway, occurs in all human malignancies. Therefore, studies of the role of Rb in the cell should lead to a further understanding of the processes of both cellular differentiation and malignant transformation. The investigators have previously shown that the Rb is a transcriptional repressor that is likely to control cellular proliferation and differentiation by regulating the expression of cell cycle genes. Rb is recruited to promoters through an interaction with E2F, a transcription factor (TF) known to bind to the promoters of several cell cycle genes and, once it is tethered to a promoter by E2F, Rb can interact simultaneously with E2F and surrounding TFs.
The specific aims are to: 1) characterize the interaction between Rb and transcription factors; and 2) determine how Rb blocks interaction between transcription factors and the basal transcription complex.
