HCOM Biomedical Sciences
Life Sciences Building 229
Research Interest: Viruses, because of their limited number of genes and their total dependence on their host for successful replication, have proven to be excellent models for the study of eucaryotic gene regulation. Further, it has been documented that transcription of some of the adenovirus early genes and a number of cellular genes, including some oncogenes, is enhanced by phorbol ester tumor promoters. This discovery has been the basis for the current in vitro model for studying phorbol ester regulation of transcription. This model uses HeLa whole cell extracts and cloned promoters from phorbol ester responsive and nonresponsive genes to study transcription in an in vitro transcription system. Recently, the focus has been on efforts to activate the phorbol ester receptor, protein kinase C (PKC), present in whole cell extracts, in an effort to determine its role on transcription of genes of interest. This system has provided evidence that upon stimulation of PKC, there is a parallel increase in the transcription of adenovirus E1A gene, thus, mimicking the in vivo observation. In contrast, there is inhibition of the adenovirus VA gene. These observations allow a direct biochemical test of specificity of the induction of gene expression by phorbol esters, and should lead to an identification of target molecules whose phosphorylation by PKC might play a role in gene induction. Ultimately, this work should provide the basis for a model to define the molecular basis for transmembrane signaling by substances which affect gene regulation. In addition, the knowledge gained from studies on the regulation of viral and cellular genes could provide the basis for designing substances that could selectively inhibit the regulation of viral genes.