Deregulation of cyclin-dependent kinase 2 activity correlates with UVC-induced apoptosis in Chinese hamster ovary cells.
Progression through the cell cycle relies on the activities of cyclin-dependent kinases (Cdk), which in turn are modulated by inhibitory proteins such as p21(waf1/cip1) that are induced when genomic damage occurs. In this study, we show that exposure of normal mammalian cells, such as NIH3T3 fibroblasts, to UVC (25 J/m2, at 254 nm) induces the expression of p21 without causing significant apoptosis, whereas similar treatment of Chinese hamster ovary (CHO-K1) cells with UVC causes apoptosis without inducing p21. The absence of p21 in UV-irradiated CHO-K1 cells is accompanied by the deregulation of Cdk2 activity. The elevation of Cdk2 activity correlates with the increase of UV-induced apoptosis, which can be suppressed by small-molecule Cdk2 inhibitors such as roscovitine and pyrrolidine dithiocarbamate. The results of this study suggest that the deregulation of Cdk2 activity may be critical to UV-induced apoptosis in CHO-K1 cells.
Liao
Chu-Bin
CB
Department of Life Science, National Tsing-Hua University, Hsin-Chu, Taiwan 30043.
Chang
Yu-Ching
YC
Kao
Chien-Wen
CW
Taniga
Ezhilan Sathyapriya
ES
Li
Hsun
H
Tzang
Bor-Show
BS
Liu
Yin-Chang
YC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D042846:CDC2-CDC28 Kinases; D016466:CHO Cells; D006224:Cricetinae; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects*; D051379:Mice; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014466:Ultraviolet Rays
D011687:Purines; D013859:Thiocarbamates; D000077546:Roscovitine; C066229:prolinedithiocarbamate; D011392:Proline; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4