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  • The EMBO Journal (2003) 22, 1567 - 1578
  • doi:10.1093/emboj/cdg157

p53 activates ICAM-1 (CD54) expression in an NF-kappaB-independent manner

Vassilis G. Gorgoulis1, Panayotis Zacharatos1, Athanassios Kotsinas1, Dimitris Kletsas2, George Mariatos1, Vassilis Zoumpourlis3, Kevin M. Ryan4, Christos Kittas1 and Athanasios G. Papavassiliou5

  1. Department of Histology–Embryology, Molecular Carcinogenesis Group, Medical School, University of Athens, 11527 Athens, Greece
  2. Laboratory of Cell Proliferation and Ageing, Institute of Biology, NCSR 'Demokritos', 15310 Athens, Greece
  3. Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece
  4. Cancer Research UK Beatson Laboratories, Glasgow G61 1BD, UK
  5. Department of Biochemistry, School of Medicine, University of Patras, 26110 Patras, Greece

Correspondence to:

Athanasios G. Papavassiliou, E-mail: papavas@med.upatras.gr

Received 8 August 2002; Accepted 12 February 2003; Revised 12 November 2002

Intercellular adhesion molecule-1 (ICAM-1) is a crucial receptor in the cell–cell interaction, a process central to the reaction to all forms of injury. Its expression is upregulated in response to a variety of inflammatory/immune mediators, including cellular stresses. The NF-kappaB signalling pathway is known to be important for activation of ICAM-1 transcription. Here we demonstrate that ICAM-1 induction represents a new cellular response to p53 activation and that NF-kappaB inhibition does not prevent the effect of p53 on ICAM-1 expression after DNA damage. Induction of ICAM-1 is abolished after treatment with the specific p53 inhibitor pifithrin-alpha and is abrogated in p53-deficient cell lines. Furthermore, we map two functional p53-responsive elements to the introns of the ICAM-1 gene, and show that they confer inducibility to p53 in a fashion similar to other p53 target genes. These results support an NF-kappaB-independent role for p53 in ICAM-1 regulation that may link p53 to ICAM-1 function in various physiological and pathological settings.

  • Keywords:

    • cellular stress,
    • ICAM-1,
    • immune response,
    • NF-kappaB,
    • p53