The basic region/helix-loop-helix/leucine repeat transcription factor USF interferes with Ras transformation

Upstream stimulatory factor (USF) is a transcription factor of the basic region/helix-loop-helix/leucine repeat family. It shares the same DNA-binding sequence as the myc oncogene. Based on the three-dimensional structures, its DNA-binding domain is structurally related to that of Max, the partner of Myc. In addition, USF can form heterodimers with a related factor, Fos-interacting protein/upstream stimulatory factor 2 (FIP/USF2), which has been shown to directly interact with Fos. In view of the provocative relationship of USF with ether factors involved in cell proliferation, we investigated whether USF could also play a role in cellular growth control. In this study, we report that USF is not an oncogene, but interferes with Ras-driven transformation. This inhibitory effect is independent of USF transactivating domains, but requires its DNA-binding activity. However, the minimal USF DNA-binding domain does not display this inhibitory effect, and even slightly enhances Ras transformation. On the basis of these data, we propose that USF may play an important role in the control of cell growth and proliferation, through both binding to promoter sequences and specific protein/protein interactions.