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

Abstract

The Y-box binding protein, YB-1, belongs to a family of multifunctional proteins which regulate gene expression on both transcriptional and translational levels. The tumor suppressor gene p53 displays growth suppressive properties by regulating gene expression through transcriptional regulation. We now demonstrate that YB-1 directly interacts with p53 using an in vitro pull-down assay. Using immunochemical co-precipitation methods, we also found that the two proteins are bound in vivo. Deletion analysis showed that three independent domains of YB-1, one at the N-terminal and two at the Cterminal, interact with p53. Conversely, a 14 amino acid sequence at the C-terminal of p53 was required for its interaction with YB-1. Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-speci®c DNA binding of p53 to its consensus sequence. By contrast, this interaction inhibited the binding of YB-1. Using a p53-responsive p21 promoter linked to a reporter gene, it can be shown that antisense expression of YB-1 inhibits the induction of this promoter by p53 in transient transfection assays. These ®ndings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction. Oncogene (2000) 19, 6194 ± 6202.

Differential antiproliferative mechanisms of novel derivative of benzimidazo[1,2-α]quinoline in colon cancer cells depending on their p53 status

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Twist and p53 reciprocally regulate target genes via direct interaction

“…Interaction between Twist and p53 M Shiota et al GST-p53 can specifically bind to the consensus sequence in the presence of pAb421 (Okamoto et al, 2000). Twist was able to inhibit the DNA binding of p53 in a dose-dependent manner ( Figure 4b, left panel).…”

Some p53-binding proteins that can function as arbiters of life and death

“…This occurs through an interaction with the C-terminus between amino-acid residues 363-376, 47 a region that is extensively modified, and which, at least in vitro is important in regulating p53 function (see elsewhere in this issue). Inhibition of YB1 has been shown to upregulate p21 Waf1/Cip1 expression, 47 although in a separate study, inhibition of YB1 led to p53-dependent apoptosis in several human cancer cell lines. 48 The reported antiapoptotic activity 49 of p21 Waf1/Cip1 would seem to be inconsistent between these two sets of observations.…”