The fate of p21CDKN1A in cells surviving UV-irradiation.
p21(CDKN1A) is a critical regulator of cell cycle progression in response to DNA damage. There are conflicting conclusions as to whether p21(CDKN1A) levels increase or decrease after ultraviolet (UV)-irradiation and recently it was even reported to disappear entirely following 2.5-30 Jm(-2) of UV-irradiation in the presence of growth medium. The latter would suggest an alternative mechanism for cell cycle arrest after UV-irradiation, since p21(CDKN1A) induction has been considered to be the major mediator of p53-mediated cell cycle arrest after DNA damage. Using physiological UV doses based on cell-killing, we previously observed and here verify that low doses (1.2-6 Jm(-2)) induce p21(CDKN1A) immediately after UV-irradiation, though higher doses cause a latency during which p21(CDKN1A) levels remain fairly constant before increasing. As expected, p53 induction preceded p21(CDKN1A) induction at all doses. Thus, p21(CDKN1A) levels after low doses of UV-irradiation may be controlled in a p53-dependent manner without severe reduction. We propose that physiological relevant UV doses should be determined for each target cell type prior to studying UV-induced responses and that p21(CDKN1A) is indeed critical for cell cycle arrest in cells that survive UV-irradiation.
Itoh
Toshiki
T
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, 94720-3202, USA. toshiki-ito@uiowa.edu
Linn
Stuart
S
D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
C493956:CDKN1A protein, human; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53