How transcriptional activators bind target proteins

The product of the proto-oncogene c-myc influences many cellular processes through the regulation of specific target genes. Through its transactivatio n domain (TAD), c-Myc protein interacts with several transcription factors, including TATA-binding protein (TBP). We present data that suggest that in contrast to some other transcriptional activators, an extended length of t he c-Myc TAD is required for its binding to TBP. Our data also show that th is interaction is a multistep process, in which a rapidly forming low affin ity complex slowly converts to a more stable form. The initial complex form ation results from ionic or polar interactions, whereas the slow conversion to a more stable form is hydrophobic in nature. Based on our results, we s uggest two alternative models for activation domain/target protein interact ions, which together provide a single universal paradigm for understanding activator-target factor interactions.