Nucleolar p120 is expressed as a delayed early response gene and is inducible by DNA‐damaging agents

Regulation of the expression of the growth‐related nucleolar p120 protein was examined in serum‐deprived and stimulated nontransformed and SV40‐transformed WI‐38 human fibroblasts. In quiescent cells, transcriptional activity of the p120 gene was very low or undetectable, and the steady‐state levels of the p120 mRNA and the p120 protein were also negligible. The transient expression of the p120 gene in the cell cycle was detected in middle G₁‐phase after the expression of the early response genes and before the expression of the DNA‐synthesis genes. Protein synthesis was required for the induction of p120 expression in serumstimulated cells. The increased level of p120 mRNA in middle G₁‐phase was attributed to an increased transcription rate of the p120 gene, and not to a change in p120 mRNA stability. The calculated half‐life of p120 mRNA was unchanged (1.8 ± 0.2 hr) in all four cell conditions tested; i.e., in middle G₁‐ or S‐phase cells and in exponentially growing normal or transformed cells. Transcription rate of the p120 gene was correlated with the steady‐state levels of either p120 protein or p120 mRNA. A sharp increase in p120 mRNA level occurred in both normal and transformed cells treated with actinomycin D used to examine p120 mRNA stability. This induction of p120 mRNA expression was seen in early G₁‐phase, but not in quiescent cells, or in middle to late G₁‐phase when cells expressed the highest level of p120 mRNA. The same expression pattern was seen by treatment with chlorambucil, another DNA‐damaging agent. The conclusions of these studies are that the expression of p120 (1) is serum inducible in a fashion characteristic of the delayed early response gene products, (2) requires the presence of newly synthesized proteins, (3) is regulated transcriptionally, and (4) can be induced by DNA‐damaging agents. © 1995 Wiley‐Liss, Inc.