Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein

Exp Cell Res. 2002 Apr 1;274(2):246-53. doi: 10.1006/excr.2002.5468.

Abstract

Hsp70 family member mot-2/mthsp70/GRP75/PBP74 was shown to bind to the tumor suppressor protein p53. In this study, by in vivo coimmunoprecipitation of mot-2 with p53 and its deletion mutants, the mot-2 binding site of p53 was mapped to its C-terminal amino acid residues 312-352, a region of p53 that includes its cytoplasmic sequestration domain. These data demonstrate that cytoplasmic sequestration and inactivation of p53 by mot-2 occurs by its binding to the cytoplasmic sequestration domain. Therefore, perturbation of mot-p53 interactions can be employed to abrogate cytoplasmic retention of wild-type p53 in tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites / physiology
  • COS Cells
  • Cell Compartmentation / physiology*
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic / metabolism*
  • Cytoplasm / metabolism*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic / physiology*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Mice
  • Mitochondrial Proteins
  • Mutation / physiology
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Protein Structure, Tertiary / physiology
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • DNA-Binding Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA9 protein, human
  • Hspa9-ps1 protein, mouse
  • Mitochondrial Proteins
  • Tumor Suppressor Protein p53