NSF Award
9317243
9317243 Berger Adaptors are transcription factors that strengthen the action of transactivators by physically bridging or guiding protein interactions with the basal transcription apparatus. The proposed research will focus on the mechanism of action of adaptors, to determine their physical role in the transcription complex and how they contribute to gene regulation. Specific experimental objectives are to dissect the domain structure of ADAs using in vivo and in vitro analyses, to determine whether ADA2 physically interacts with the acidic activation domain of the herpes virus transactivator VP16, and to identify specific amino acid contacts between ADA2 and VP16 using classic genetic suppression of substitution mutations in VP16. %%% A crucial cellular regulatory step is the decision to turn specific genes on and off. I am interested in the basic principles that underlie this regulation of gene expression, and the general mechanisms that may be common to all genes. We are using a simple model system for studying gene expression, namely Saccharomyces cerevisiae, or baker's yeast. Yeast is an increasingly powerful research tool for the study of basic cellular processes, because of its unique experimental accessibility and because the function of many regulatory proteins is highly conserved in evolution, even between yeast and humans. Several separate classes of factors are required for genes to be expressed. These factors must physically interact and these contacts have been the focus of intense interest, since identification of the precise factors and how they interact will help to explain the mechanics of the process. We have previously established that a novel class of factors, termed adaptors, are important for these physical interactions. We devised a method in yeast to isolate the genes for adaptors and have cloned and characterized two components of an adaptor. Future objectives are to dissect the structure of the adaptor, and to analyze it s physical and functional role in the gene expression process. These particular adaptors may be representative of a large class of factors, and thus, as a class, may be fundamentally important to gene regulation. ***
