mRNA Levels For Human Nucleolar Protein P120 in Tumor and Nontumor Cells

Hazlewood, Jeff; Fónagy, A; Henning, Dale; Freeman, James W.; Busch, Rose K.; Busch, Harris

doi:10.3727/095535489820875426

Cited by 16 publications

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“…Only a few other mammalian proteins have been implicated in rRNA processing to date, based on the function of their yeast homologs. For example, p120 was originally identified as a tumor proliferation antigen (33) and was later implicated in rRNA processing, since deletion of its yeast homolog, Nop2p, causes a block in the processing of the 27S pre-rRNA to the mature 25S rRNA (36). Consistent with a role in rRNA processing, p120 was shown to cofractionate with the 60-80S preribosomal particles in HeLa cell extracts (30).…”

Section: Discussionmentioning

confidence: 65%

“…(34,36,66). The total number of nonribosomal proteins involved in rRNA processing is unknown but is likely to be large, as underscored by the complexity of eukaryotic rRNA modification, processing, and ribosome assembly.In mammalian systems, relatively few nonribosomal nucleolar proteins have been characterized; the best-studied examples include fibrillarin, a common component of the snoRNPs (43, 53); nucleolin (C23), a pre-rRNA binding protein with multiple functions in processing and ribosome assembly (29,55,77); B23, associated with ribosome assembly at later stages of maturation (11); and p120, a nucleolar RNA binding protein that cofractionates with 60S-80S pre-rRNA particles (30,33). In comparison with yeast, the majority of the molecular players in the mammalian rRNA processing machinery remain un-…”

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confidence: 99%

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Bop1 Is a Mouse WD40 Repeat Nucleolar Protein Involved in 28S and 5.8S rRNA Processing and 60S Ribosome Biogenesis

Strezoska

Pestov

Lau

2000

Molecular and Cellular Biology

166

182

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We have identified and characterized a novel mouse protein, Bop1, which contains WD40 repeats and is highly conserved through evolution. bop1 is ubiquitously expressed in all mouse tissues examined and is upregulated during mid-G 1 in serum-stimulated fibroblasts. Immunofluorescence analysis shows that Bop1 is localized predominantly to the nucleolus. In sucrose density gradients, Bop1 from nuclear extracts cosediments with the 50S-80S ribonucleoprotein particles that contain the 32S rRNA precursor. RNase A treatment disrupts these particles and releases Bop1 into a low-molecular-weight fraction. A mutant form of Bop1, Bop1⌬, which lacks 231 amino acids in the N-terminus, is colocalized with wild-type Bop1 in the nucleolus and in ribonucleoprotein complexes. Expression of Bop1⌬ leads to cell growth arrest in the G 1 phase and results in a specific inhibition of the synthesis of the 28S and 5.8S rRNAs without affecting 18S rRNA formation. Pulse-chase analyses show that Bop1⌬ expression results in a partial inhibition in the conversion of the 36S to the 32S pre-rRNA and a complete inhibition of the processing of the 32S pre-rRNA to form the mature 28S and 5.8S rRNAs. Concomitant with these defects in rRNA processing, expression of Bop1⌬ in mouse cells leads to a deficit in the cytosolic 60S ribosomal subunits. These studies thus identify Bop1 as a novel, nonribosomal mammalian protein that plays a key role in the formation of the mature 28S and 5.8S rRNAs and in the biogenesis of the 60S ribosomal subunit.Biogenesis of the eukaryotic ribosomes occurs in the nucleolus, a complex nuclear organelle that forms around the nucleolar organizer regions located in heterochromatic chromosomal sites containing multiple rRNA genes (69, 81). The organization of the nucleolus and the assembly of ribosomes are coupled to transcription of rDNA by RNA polymerase I, which synthesizes a large primary precursor transcript. This precursor transcript is then processed into the mature 18S, 5.8S, and 28S/25S rRNAs. These rRNAs are assembled into preribosomes with some 80 ribosomal proteins that are transported into the nucleus, and with the 5S rRNA, transcribed by RNA polymerase III outside of the nucleolus (28). A large number of small nucleolar RNAs (snoRNAs) and nonribosomal proteins are also recruited to the nucleolus to participate in the modification, processing, and assembly of the rRNAs and proteins into ribonucleoprotein (RNP) particles. These preribosomal RNP (pre-rRNP) particles mature into nearly complete ribosomal subunits prior to their export out of the nucleus.Upon synthesis, the primary precursor rRNA transcript is modified by ribose methylation and pseudouridine conversion and processed through a series of nucleolytic cleavages into the matured rRNAs (21) (see Fig. 6). In vertebrates, the arrangement of the 47S primary precursor transcript begins with a 5Ј external transcribed spacer (5Ј-ETS), followed by the 18S rRNA, internal transcribed spacer 1 (ITS1), 5.8S rRNA, internal transcribed spacer 2 (ITS2), 28S rRNA, and t...

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Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

Bop1 Is a Mouse WD40 Repeat Nucleolar Protein Involved in 28S and 5.8S rRNA Processing and 60S Ribosome Biogenesis

Strezoska

Pestov

Lau

2000

Molecular and Cellular Biology

166

182

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“…D: The percents of protein P120 mAb reactive cells. the nucleolar residue fraction by biochemical preparation (Freeman et al, 19891, and in a novel microfibrillar structure in the nucleolar matrix by electronmicroscopy (Ochs et al, 1988). Speculation can only be made whether P120 protein plays a role in DNA replication directly due to the high amount of P120 protein present in S-phase, or whether P120 protein regulates entry into S-phase, before the restriction point, a few hours prior to S-phase (Pardee, 1974).…”

Section: Time After Release (Hrs)mentioning

confidence: 99%

Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts

Fónagy

Swiderski

Wilson

et al. 1993

Journal Cellular Physiology

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Normal and SV40 virus-transformed WI-38 human lung fibroblasts were serum starved and refed, or synchronized by double thymidine block and released from the block. At different time points in the cell cycle, steady state levels of P120 mRNA and P120 protein content of the cells were determined by densitometric scans of Northern and Western blots. At the same time points, [3H]thymidine uptake was measured and flow cytometric analysis performed for DNA content and P120 antigen staining. Levels of P120 protein and P120 mRNA were approximately 4 times greater in non-synchronous, exponentially growing transformed cells than in similarly growing normal cells. Early G1-phase cells, synchronized either with serum deprivation or with metabolic block, contained only a trace amount of P120 protein and mRNA. The P120 gene was transcribed early in G1 and P120 protein synthesis initiated in middle G1. A dramatic increase of P120 protein level occurred in S-phase with a corresponding mRNA peak preceding the P120 protein peak. These results indicate that P120 is overexpressed in transformed WI-38 cells and that P120 is temporally regulated during the cell cycle of both transformed and normal fibroblasts. The dramatic increase in P120 protein expression at the G1 to S boundary suggests that P120 may play a role in the regulation of cell cycle and increased nucleolar activity that is associated with cell proliferation.

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“…In this report we present evidence that the transient expression of the p120 gene is transcriptionally regulated in the cell cycle. Therefore, the high transcription rate of the p120 gene is responsible for the elevated levels of p120 mRNA and p120 protein found characteristically in exponentially growing transformed cells and in cells in late GIor S-phase as compared to exponentially growing nontransformed cells (Freeman et al, 1988;Hazlewood et al, 1989;Fonagy et al, 1993Fonagy et al, , 1994Fonagy et al, , 1995. On the basis of the rapid p120 mRNA elevation measured in the cells after treatment with protein or RNA synthesis inhibitor, we suggest a negative transcriptional regulation of the p120 gene expression and a possible role for p120 protein in repair processes.…”

Section: Discussionmentioning

confidence: 99%

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

Fónagy

Swiderski

Freeman

1995

Journal Cellular Physiology

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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.

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mRNA Levels For Human Nucleolar Protein P120 in Tumor and Nontumor Cells

Cited by 16 publications

References 0 publications

Bop1 Is a Mouse WD40 Repeat Nucleolar Protein Involved in 28S and 5.8S rRNA Processing and 60S Ribosome Biogenesis

Bop1 Is a Mouse WD40 Repeat Nucleolar Protein Involved in 28S and 5.8S rRNA Processing and 60S Ribosome Biogenesis

Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts

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

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