Identification of p53-dependent genes potentially involved in UVB-mediated premature senescence of human skin fibroblasts using siRNA technology.
Premature senescence of skin human diploid fibroblasts is induced after a series of 10 sublethal exposures to UVB at 2.5 kJ/m(2) with appearance of several biomarkers of cellular senescence like senescence-associated beta-galactosidase activity (SA beta-gal) and cell cycle arrest. Herein it is shown that the induction of UVB-induced premature senescence is associated with a transient increase of protein abundance and DNA-binding activity of p53. Silencing p53 expression with small interfering RNA (siRNA) affected the basal level of SA beta-gal and proliferative potential, but did not prevent UVB-induced increase of SA beta-gal and decrease of DNA synthesis. We used a senescence-specific low-density DNA array and p53 siRNA to study the mRNA abundance of 240 senescence-related genes and identified several potential p53-dependent genes differentially expressed after the repeated exposures to UVB.
Borlon
Céline
C
Research Unit on Cellular Biology (URBC), Department of Biology, Faculty of Sciences, University of Namur (FUNDP), Rue de Bruxelles, 61, B-5000 Namur, Belgium.
Vankoningsloo
Sébastien
S
Godard
Patrice
P
Debacq-Chainiaux
Florence
F
Toussaint
Olivier
O
D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000032:analysis
D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D004247:DNA; D001616:beta-Galactosidase