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Papers In Press, published online ahead of print October 8, 2002
Department of Pharmacology, Chang Gung University, Tao Yuan, Taiwan 333
Corresponding Author: byung{at}mail.cgu.edu.tw
Nucleophosmin/B23 (NPM/B23), a nucleolar protein, was rapidly up-regulated after UV irradiation (at 254 nm; 30 J/m2) in NIH 3T3 cells and HeLa/S3 cells. Level of NPM/B23 mRNA reached the peak 45-60 min after UV treatment and returned to baseline by 12 h. Transcription inhibitor actinomycin D (5 ug/ml) prevented the UV-induced increase of NPM/B23 mRNA, suggesting that UV induction of NPM/B23 was mediated at transcriptional level. Moreover, the UV-induced NPM/B23 expression was superinduced by cycloheximide (20 ƒÝg/ml), which was a 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, MAPK, AP-1, NFƒÛB, and DNA dependent kinase. Our results indicate that UV stimulation of NPM/B23 expression is mediated through a novel UV-inducible pathway, and is an immediate-early gene response induced by damaged DNA. Induction of immediate-early gene may be 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.
J. Biol. Chem, 10.1074/jbc.M206550200
Submitted on July 2, 2002
Revised on October 8, 2002
Accepted on October 8, 2002
UV stimulation of nucleophosmin/B23 expression is an immediate-early gene response induced by damaged DNA
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