A p53-independent pathway for induction of p21waf1cip1 and concomitant G1 arrest in UV-irradiated human skin fibroblasts.
Largely on the basis of studies using the potent clastogen ionizing radiation, it has been widely assumed that up-regulation of the cyclin-dependent kinase inhibitor p21(waf1cip1) in cultured cells exposed to DNA-damaging agents is contingent upon the presence of functional p53 tumor suppressor protein. Nevertheless, we demonstrate here that the model mutagen 254-nm UV light induces p21(waf1cip1) protein and concomitant G1 arrest in normal human skin fibroblasts, as well as in p53-deficient fibroblasts derived from cancer-prone Li-Fraumeni syndrome patients. However, as expected, following exposure to ionizing radiation, elevated p21(waf1cip1) protein levels and G1 arrest were observed only in normal fibroblasts. These data provide a prominent and clinically relevant example in which p21(waf1cip1)-mediated growth arrest occurs independently of p53 in human cells treated with a model DNA-damaging agent.
Loignon
M
M
Centre de Recherche Guy Bernier, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
Fetni
R
R
Gordon
A J
AJ
Drobetsky
E A
EA
D000782:Aneuploidy; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D016193:G1 Phase / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D011123:Polyploidy; D016196:S Phase / Q000235:genetics / Q000528:radiation effects; D012867:Skin / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53