Dose-dependent changes in cyclin D1 in response to 4-nitroquinoline 1-oxide-induced DNA damage.
Cells respond to DNA damage by either repairing the damage or committing to a death or senescence pathway, dependent on the level of damage sustained. In this study, we show that the protein levels of cyclin D1 and the CDK inhibitor, p21(CIP1), respond in a dose-dependent manner to the DNA damaging agent, 4-nitroquinoline 1-oxide (4NQO). Cyclin D1 responses were independent of p53 and resulted in a partial loss of Retinoblastoma protein phosphorylation. The differential responses of cyclin D1 and p21(CIP1) were associated with distinct cellular responses: in low dose treatments the cells recovered after a lag period whilst at medium and high doses, the cells died through seemingly distinct mechanisms. Our data suggest that the balance between cyclin D1 and p21(CIP1) following exposure to DNA damage may play a key role in determining the subsequent cellular responses.
Suwaki
Natsuko
N
Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Child
Emma S
ES
Elphick
Lucy M
LM
Mann
David J
DJ
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D019938:Cyclin D1 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009153:Mutagens / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009153:Mutagens; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D015112:4-Nitroquinoline-1-oxide