p53 activates ICAM-1 (CD54) expression in an NF-kappaB-independent manner.
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.
Gorgoulis
Vassilis G
VG
Department of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, University of Athens, 11527 Athens.
Zacharatos
Panayotis
P
Kotsinas
Athanassios
A
Kletsas
Dimitris
D
Mariatos
George
G
Zoumpourlis
Vassilis
V
Ryan
Kevin M
KM
Kittas
Christos
C
Papavassiliou
Athanasios G
AG
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D008969:Molecular Sequence Data; D009153:Mutagens / Q000633:toxicity; D016328:NF-kappa B / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D017931:DNA Primers; D009153:Mutagens; D016328:NF-kappa B; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D018799:Intercellular Adhesion Molecule-1