The long term goal of this research program is to understand the process of transcription, and specifically how promoter-specific activator proteins direct the transcription of the TATA-containing adenovirus genes. We hypothesize that the AdV integrator proteins form a heteromeric complex with the general transcription factor TFIIB. As part of this process, integrator proteins mediate the recruitment of TFIIB to the AdV major late promoter (MLP). The specific aims of this proposal are (1) to clone, purify and characterize the AdV integrator proteins. These proteins will be purified and their ability to mediate TATA-dependent transcription in vitro will be tested; (2) to generate antisera against the integrator proteins; and (3) to generate cell lines that express functional integrator proteins. These cell lines will be tested for their ability to complement for the function of integrator function. Based on our progress during the current funding period, these objectives are within reach. We will take advantage of recent advances in the understanding of AdV integrator proteins to accomplish the goals of this research program. The integrator proteins are responsible for the regulation of transcription by cellular and viral TATA-containing promoters. The proposed research program focuses on the molecular events that occur during transcription initiation in the context of the major late promoter of AdV. Elucidating the molecular events that regulate transcription of cellular and viral TATA-containing promoters is important to understand the mechanism of promoter activation, a process that is essential for growth and development in all organisms. These studies may lead to a better understanding of the events that are associated with a number of congenital, developmental, and neoplastic diseases, including cancer.