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

Oncogene. 2000 Dec 14;19(54):6194-202. doi: 10.1038/sj.onc.1204029.

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 C-terminal, 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-specific 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 findings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Consensus Sequence
  • DNA-Binding Proteins*
  • Humans
  • NFI Transcription Factors
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Protein Structure, Tertiary
  • Sequence Deletion
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Y-Box-Binding Protein 1

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • NFI Transcription Factors
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Y-Box-Binding Protein 1
  • YBX1 protein, human