Rapid downregulation of cyclin D1 mRNA and protein levels by ultraviolet irradiation in murine macrophage cells.
DNA damage causes G1 cell cycle arrest through stabilization of p53 and its induction. As this process requires transcription, it takes several hours to achieve cell cycle arrest. We observed that ultraviolet (UV) light induces an immediate G1 arrest by rapid clearance of cyclin D1 in the murine macrophage cell line Bac1.2F5. The rapid disappearance of the cyclin D1 protein after exposure to UV was caused by at least two different mechanisms. In the first mechanism, cyclin D1 mRNA promptly disappeared within 1 min after UV irradiation, although cdk4 mRNA levels were unchanged. In the second mechanism, UV irradiation accelerated the degradation of cyclin D1 protein through the proteasome pathway. The half-life of the cyclin D1 protein was measured by pulse chase analysis and was shortened by UV light. These findings suggest that in the UV-irradiated Bac1.2F5 cells the amount of cyclin D1 protein is regulated at both the mRNA and protein levels. These two clearance mechanisms were also observed in murine bone-marrow-derived macrophages from wild type and p53 -/- mice, indicating that cyclin D1 mRNA and protein levels are independent of p53 function. This machinery might contribute to G1 cell cycle arrest and prevent cells from accumulating further DNA damage.
Miyakawa
Y
Y
Molecular Oncology Group, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa, 247, Japan. yoshi@med.keio.ac.jp
Matsushime
H
H
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004249:DNA Damage; D015536:Down-Regulation / Q000528:radiation effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D020871:RNA Stability / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D020413:3' Untranslated Regions; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex