On another front, ets proteins are controlled by cell signaling cascades. We are investigating the activation and inhibition of the function of ets proteins in T lymphocytes by several phosphorylation events. Finally, every ets protein functions in association with at least one additional transcription factor. We are developing molecular models for how protein partnerships can regulate the specificity of action of ets genes. The issue of transcription factor specificity is central to the control of cell growth and differentiation and the misregulation of these processes during oncogenesis.
Nuclear oncogenes are most often transcription factors that cause inappropriate gene expression.
The ets family illustrates this oncogenic potential. Members of the family are the transducing oncogenes of several acute-transforming retroviruses. Furthermore, human chromosome translocations involving six different ets genes cause a variety of leukemias and other human cancers. In these diseases, it is proposed that regulation of gene expression by the ets proteins is perturbed. We hope to decipher the molecular mechanism by which these oncogenic ets proteins dysregulate gene expression.