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p53 activates ICAM-1 (CD54) expression in an NF-kappaB-independent manner
Vassilis G Gorgoulis1, Panayotis Zacharatos, Athanassios Kotsinas
1Department of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, University of Athens, 11527 Athens.
Abstract:
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.
Insights
The study reveals that p53 activation, independent of NF-kappaB, induces Intercellular Adhesion Molecule-1 (ICAM-1) expression following DNA damage. This finding links p53 to ICAM-1 regulation in cellular injury responses.
Area of Science:
- Molecular Biology
- Cellular Biology
- Immunology
Background:
- Intercellular Adhesion Molecule-1 (ICAM-1) is vital for cell-cell interactions and injury response.
- ICAM-1 expression increases with inflammatory mediators and cellular stress.
- The NF-kappaB pathway is recognized for activating ICAM-1 transcription.
Purpose of the Study:
- To investigate the role of p53 in ICAM-1 induction.
- To determine if p53's effect on ICAM-1 is independent of NF-kappaB signaling.
- To identify p53-responsive elements within the ICAM-1 gene.
Main Methods:
- Utilized p53 inhibitor pifithrin-alpha.
- Examined ICAM-1 expression in p53-deficient cell lines.
- Mapped p53-responsive elements in ICAM-1 gene introns.
Main Results:
- p53 activation induces ICAM-1 expression independently of NF-kappaB.
- p53 inhibition abolished ICAM-1 induction.
- p53-deficient cells showed abrogated ICAM-1 induction.
- Two intronic p53-responsive elements were identified in the ICAM-1 gene.
Conclusions:
- p53 plays an NF-kappaB-independent role in regulating ICAM-1.
- This pathway may connect p53 function to ICAM-1 roles in physiology and pathology.