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

Abstract

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 serum-stimulated 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.

Nuclear GIT2 Is an ATM Substrate and Promotes DNA Repair

“…In addition, overexpression of GIT2 increased the expression of SPEN and NOP2, proteins that are involved in stress-responsive polyadenylated RNA metabolism (49), nuclear responses to cytotoxic DNA damage (42,50), as well as aging and neurodevelopmental processes (43) (see Fig. S3 in the supplemental material).…”

Role of RNA methyltransferases in tissue renewal and pathology

“…NOP2 (NSun1) is nucleolar protein that binds to 60–80S pre-ribosomal particles and is mainly described for its function in regulating cell proliferation and is up-regulated in response DNA damaging agents [ 41,42 ]. Whether NOP2 methylates ribosomal RNA has yet to be confirmed.…”

Superinduction of P‐glycoprotein messenger RNA in vivo in the presence of transcriptional inhibitors

“…The phenomenon of superinduction of mRNAs upon treatment with protein synthesis inhibitors or transcriptional inhibitors has been reported previously, especially in cell lines. Transcriptional inhibitors have been shown to induce and stabilize a subset of mRNAs (45–49). Thus it has been proposed that the superinduction by transcriptional inhibitors could be due to the blockage of expression of a factor involved in mRNA degradation.…”