Regulation of MCP-1 chemokine transcription by p53

Katrin Hacke, Bladimiro Rincon-Orozco, Gilles Buchwalter, Simone Y. Siehler, Bohdan Wasylyk, Lisa Wiesmüller, Frank Rösl

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Background: Our previous studies showed that the expression of the monocyte-chemoattractant protein (MCP)-1, a chemokine, which triggers the infiltration and activation of cells of the monocyte-macrophage lineage, is abrogated in human papillomavirus (HPV)-positive premalignant and malignant cells. In silico analysis of the MCP-1 upstream region proposed a putative p53 binding side about 2.5 kb upstream of the transcriptional start. The aim of this study is to monitor a physiological role of p53 in this process.Results: The proposed p53 binding side could be confirmed in vitro by electrophoretic-mobility-shift assays and in vivo by chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-α can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-α treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-α addition, directly confirming a crosstalk between p53 and MCP-1.Conclusion: These data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment.

Original languageEnglish (US)
Article number82
JournalMolecular Cancer
Volume9
DOIs
StatePublished - Apr 20 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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    Hacke, K., Rincon-Orozco, B., Buchwalter, G., Siehler, S. Y., Wasylyk, B., Wiesmüller, L., & Rösl, F. (2010). Regulation of MCP-1 chemokine transcription by p53. Molecular Cancer, 9, [82]. https://doi.org/10.1186/1476-4598-9-82