The Y-box-binding Protein, YB1, Is a Potential Negative Regulator of the p53 Tumor Suppressor

The p53 tumor suppressor plays a major role in preventing tumor development by transactivating genes to remove or repair potentially tumorigenic cells. Here we show that the Y-box-binding protein, YB1, acts as a negative regulator of p53. Using reporter assays we show that YB1 represses transcription of the p53 promoter in a sequence-specific manner. We also show that YB1 reduces endogenous levels of p53, which in turn reduces p53 activity. Conversely, inhibiting YB1 in a variety of tumor cell lines induces p53 activity, resulting in significant apoptosis via a p53-dependent pathway. These data suggest that YB1 may, in some situations, protect cells from p53-mediated apoptosis, indicating that YB1 may be a good target for the development of new therapeutics.