Tumor suppressor p53 protein is a new target for the metastasis-associated Mts1/S100A4 protein. Functional consequences of their interaction

Mariam Grigorian, Susanne Andresen, Eugene Tulchinsky, Marina Kriajevska, Charlotte Carlberg, Charlotte Kruse, Martin Cohn, Noona Ambartsumian, Annette Christensen, Galina Selivanova, Eugene Lukanidin

Research output: Contribution to journalArticlepeer-review

254 Citations (Scopus)

Abstract

A physical and functional interaction between the Ca2+-binding protein Mts1 (S100A4) and the tumor suppressor p53 protein is shown here for the first time. We demonstrate that Mts1 binds to the extreme end of the C-terminal regulatory domain of p53 by several in vitro and in vivo approaches: co-immunoprecipitation, affinity chromatography, and far Western blot analysis. The Mts1 protein in vitro inhibits phosphorylation of the full-length p53 and its C-terminal peptide by protein kinase C but not by casein kinase II. The Mts1 binding to p53 interferes with the DNA binding activity of p53 in vitro and reporter gene transactivation in vivo, and this has a regulatory function. A differential modulation of the p53 target gene (p21/WAF, bax, thrombospondin-1, and mdm-2) transcription was observed upon Mts1 induction in tet-inducible cell lines expressing wild type p53. Mts1 cooperates with wild type p53 in apoptosis induction. Our data imply that the ability of Mts1 to enhance p53-dependent apoptosis might accelerate the loss of wild type p53 function in tumors. In this way, Mts1 can contribute to the development of a more aggressive phenotype during tumor progression.

Original languageEnglish
Pages (from-to)22699-22708
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number25
DOIs
Publication statusPublished - Jun 22 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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