| First Author | Wu MH | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 50 | Pages | 48234-40 |
| PubMed ID | 12374805 | Mgi Jnum | J:80713 |
| Mgi Id | MGI:2446969 | Doi | 10.1074/jbc.M206550200 |
| Citation | Wu MH, et al. (2002) UV stimulation of nucleophosmin/B23 expression is an immediate-early gene response induced by damaged DNA. J Biol Chem 277(50):48234-40 |
| abstractText | Nucleophosmin/B23 (NPM/B23), a nucleolar protein, was rapidly up-regulated after UV irradiation (at 254 nm; 30 J/m(2)) in NIH 3T3 cells and HeLa/S3 cells. Levels of NPM/B23 mRNA peaked 45-60 min after UV treatment and returned to baseline by 12 h. Transcription inhibitor actinomycin D (5 microg/ml) prevented the UV-induced increase of NPM/B23 mRNA, suggesting that UV induction of NPM/B23 was mediated at the transcriptional level. Moreover, UV-induced NPM/B23 expression was super-induced by cycloheximide (20 microg/ml), which was characteristic of immediate-early gene response. The transcriptional activation of NPM/B23 by UV was also confirmed by NPM/B23 promoter activity assay. Thymine dinucleotide, mimicking the effects of UV-induced DNA damage, was able to trigger NPM/B23 expression in the absence of genomic DNA damage. UV-induced activation of NPM/B23 promoter could not be blocked by UV-inducible pathway inhibitors, such as those of growth factor tyrosine kinase, mitogen-activated protein kinase, AP-1, NF-kappaB, and DNA-dependent kinase. Our results indicate that UV stimulation of NPM/B23 expression may be mediated through a novel UV-inducible pathway and is an immediate-early gene response induced by damaged DNA. Induction of immediate-early gene is an initial step in the regulation of cellular and genomic responses to external stimuli. Our results thus provide important evidence for an involvement of NPM/B23 in the acute response of mammalian cells to environmental stress. |
