Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression

The Y-box binding protein, YB-1, belongs to a family of multifunctional pro teins which regulate gene expression on both transcriptional and translatio nal levels. The tumor suppressor gene p53 displays growth suppressive prope rties by regulating gene expression through transcriptional regulation, We now demonstrate that YB-1 directly interacts with p53 using an in vitro pul l-down assay. Using immunochemical co-precipitation methods, we also found that the two proteins are bound in vivo. Deletion analysis showed that thre e independent domains of YB-1, one at the N-terminal and two at the C-termi nal, interact with p53. Conversely, a 14 amino acid sequence at the C-termi nal of p53 was required for its interaction with YB-1, Gel mobility shift a ssays showed that the interaction of YB-1 with p53 stimulated the sequence- specific DNA binding of p53 to its consensus sequence, By contrast, this in teraction inhibited the binding of YB-1, Using a p53-responsive p21 promote r linked to a reporter gene, it can be shown that antisense expression of Y B-1 inhibits the induction of this promoter by p53 in transient transfectio n assays, These findings delineate a straightforward mechanism for gene exp ression through p53-YB-1 interaction.