Our long term aim is to uncover the molecular mechanisms that mediate cell growth, differentiation and development. We believe that transcriptional regulation provides the key link in triggering the complex cellular processes required to initiate cell growth. Towards this goal we have proposed the following six projects: Project 1 - Regulation of Protooncogene Rel: Studies are designed to determine the function of protooncogene Rel in normal and transformed cells; Project 2 - Regulation of Transcription in Cycle and by Phosphorylation: Experiments are proposed to study the role of phosphorylation in modulating the activity of transcription factors; Project 3 - Developmental Regulation of Transcription Factor CREB: This program will undertake an extensive analysis of the role of nuclear transcription factor CREB during development; Project 4 - T-Cell Specific Transcriptional _Activators and Silencers: A series of intricate experiments are proposed to study the mechanism of transcription of T-cell receptor genes; Project 5 - Transcriptional Regulation of T-Cell Receptor alpha Gene: This proposal is devoted to understanding how transcriptional enhancer sequences situated at considerable distance from the promoters are able to influence transcription; and Project 6 - Interaction of nuclear receptors and AP-l Regulatory Networks: An indepth examination of the antagonistic relationship at the transcriptional level between steroid receptor response elements and nuclear oncoproteins Fos and Jun are planned. The work proposed in the six projects will rely heavily on the availability of the core facilities. We submit that the various programs proposed here will benefit enormously from intellectual interactions among the participants and shared resources.
