THE ROLE OF THE CARBOXY-TERMINUS OF V-REL IN TRANSFORMATION AND ACTIVATION OF ENDOGENOUS GENE-EXPRESSION

Proteins within the Rel/NF-kappa B transcription factor family can be divided into two functional domains, a homologous amino terminal regio n, the Rel Homology Domain, and a divergent carboxy terminal domain. T he amino terminal sequences specify DNA binding, nuclear localization, and interaction with the I kappa B family of inhibitory proteins. The carboxy terminus of each protein functions as a transcriptional activ ation domain, however, precise definition of sequence requirements has been difficult. To further define these sequences, small 100 bp delet ions were constructed throughout the carboxy terminus of v-Rel. Each r esulting mutant was assayed for DNA binding, localization, protein com plex formation, activation of endogenous gene expression and ability t o transform bone marrow cells and fibroblasts. Surprisingly, deletion within the carboxy terminus had marginal effects on transforming poten tial. However, three separate regions were required for full activatio n of gene expression. Taken together, these results suggest that the c arboxy terminus of v-Rel contains multiple sequences that participate in the activation of gene expression.