RPS19

Gene Summary

Gene:RPS19; ribosomal protein S19
Aliases: DBA, S19, DBA1
Location:19q13.2
Summary:Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S19E family of ribosomal proteins. It is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, GeneCard, Gene
Protein:40S ribosomal protein S19
HPRD
Source:NCBIAccessed: 16 March, 2015

Ontology:

What does this gene/protein do?
Show (26)
Pathways:What pathways are this gene/protein implicaed in?
Show (1)

Cancer Overview

Diamond-Blackfan Anaemia is an inherited autosomal dominant disorder of the bone marrow. Aproximately a quarter of patients have mutation of RPS19 gene. People with Diamond-Blackfan anemia have an increased risk of developing myelodysplastic syndrome, acute myeloid leukaemia and osteosarcoma

Research Indicators

Publications Per Year (1990-2015)
Graph generated 16 March 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Cancer Gene Expression Regulation
  • ribosomal protein S19
  • Diamond-Blackfan Anemia
  • Gene Expression Regulation
  • Protein Biosynthesis
  • MYC
  • Focal Nodular Hyperplasia
  • Case-Control Studies
  • Apoptosis
  • Reproducibility of Results
  • Disease Models, Animal
  • Cell Cycle
  • Cell Separation
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-myc
  • Liver Neoplasms, Experimental
  • Erythroid Precursor Cells
  • Ribosomal Proteins
  • Liver Cancer
  • Adenoma
  • Hepatocytes
  • Genome, Human
  • Hep G2 Cells
  • Mice, Transgenic
  • Transcription
  • Genome-Wide Association Study
  • Proto-Oncogene Proteins c-myb
  • Chromosome 19
  • Microarray Analysis
  • Mutation
  • RNA, Ribosomal, 18S
  • Hepatocellular Carcinoma
Tag cloud generated 16 March, 2015 using data from PubMed, MeSH and CancerIndex

Latest Publications: RPS19 (cancer-related)

Hunecke D, Spanel R, Länger F, et al.
MYC-regulated genes involved in liver cell dysplasia identified in a transgenic model of liver cancer.
J Pathol. 2012; 228(4):520-33 [PubMed] Related Publications
Foci of liver cell dysplasia (LCD) are distinct morphological entities and may evolve into hepatocellular carcinomas (HCCs). While most HCCs overexpress c-Myc, its role in LCD remains uncertain. Therefore, a c-Myc transgenic model of HCC was investigated to understand the genetic events forcing liver cells into dysplasia and subsequent malignant transformation. Specifically, whole genome scans enabled fingerprinting of genes at different stages of disease, ie LCD and HCC, while laser microdissected LCD lesions were used to validate regulation of candidate genes by quantitative real-time RT-PCR, ie Mybbp1a, Rps7, Rps19, Rpl10a, Skp1a, Tfdp1, Nhp2, and Bola2. EMSA band shift assays confirmed c-Myc DNA binding at regulatory sequences of candidate gene-specific promoters. Additionally, published ChIP-seq data helped to define the candidate genes as c-Myc bona fide targets. Treatment of the human hepatoma cell line HepG2 with hepatic growth factor (Hgf) caused c-Myc protein induction and transcriptional up-regulation of candidate genes, albeit at different levels when individual genes were compared. A significant increase of HepG2 entering the G1-phase was associated with up-regulation of the candidate genes in an Hgf concentration-dependent matter. Finally, we confirmed regulation of candidate genes in patients' samples with low- and high-grade dysplasia and HCC staged T1 to T3, while their expression was unchanged in focal nodular hyperplasia and hepatic adenoma, therefore asserting the diagnostic value and clinical significance of these candidate genes. Overall, novel c-Myc targeted genes were identified and may contribute to hepatocyte transformation by altering cell cycle control, thereby contributing to c-Myc's oncogenic activity.

Safaeian M, Hildesheim A, Gonzalez P, et al.
Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer.
PLoS One. 2012; 7(4):e33619 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer.
METHODOLOGY/PRINCIPAL FINDINGS: We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P(trend)<0.0001), and RPS19 rs2305809 (P(trend)=0.0007), respectively. Both SNPs were also associated with progression.
CONCLUSIONS/SIGNIFICANCE: These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.

Dunphy CH
Reaction patterns of TRAP and DBA.44 in hairy cell leukemia, hairy cell variant, and nodal and extranodal marginal zone B-cell lymphomas.
Appl Immunohistochem Mol Morphol. 2008; 16(2):135-9 [PubMed] Related Publications
CONTEXT: The differential diagnosis of hairy cell leukemia (HCL) includes HC variant (HC-V) and marginal zone lymphoma (MZL). There is a high sensitivity of combined DBA.44/TRAP-positivity (+) in confirming HCL. A previous study of mucosa-associated lymphoid tissue lymphoma showed DBA.44+ in 10%, TRAP+ in 29%, and DBA.44+/TRAP+ in 5%.
OBJECTIVE: We now study nodal MZL (NMZL) and HC-V.
DESIGN: Two HCL, 2 HC-V, 3 MZL of bone marrow (BM), 2 MZL versus B-cell lymphoma, not otherwise specified (BCL, NOS) of BM, and 4 NMZL and 5 extranodal MZL (EMZL) were stained with DBA.44 and TRAP and reviewed for staining pattern/intensity.
RESULTS: DBA.44 intensely stained all cells in 2/2 HCL, 1/2 HC-V, and 1 EMZL; intensely stained >20% of neoplastic cells (NCs) in 7 MZLs (1 BM, 3 NMZL, and 3 EMZL); and was negative/stained <10% of NCs in 1/2 HC-V, the remaining MZLs (2 BM, 1 NMZL, and 1 EMZL), and 2/2 MZL versus BCL, NOS-BM. TRAP intensely stained all cells in 2/2 HCL, the DBA.44+ HC-V, and 1 MZL versus BCL, NOS-BM; intensely stained >20% of NCs in 1 MZL versus BCL, NOS-BM, 1 MZL-BM, and 1 EMZL; and was negative in the remainder (1 HC-V, 2 MZL-BM, 1 MZL vs. BCL, NOS-BM, the 4 NMZL, 3 EMZL) in which it was able to be performed. There was combined DBA.44+/TRAP+ in 2/2 HCL, 1/2 HCV, 1/3 MZL-BM, and 1/5 EMZL. Only 1 case (MZL vs. BCL, NOS-BM) was TRAP+/DBA.44-.
CONCLUSIONS: Although combined intense, diffuse TRAP+/DBA.44+ is highly sensitive for HCL, it is not entirely specific, and may be observed in HC-V and EMZL, further supporting a histogenetic relationship between these entities.

Wei Q, Li M, Fu X, et al.
Global analysis of differentially expressed genes in androgen-independent prostate cancer.
Prostate Cancer Prostatic Dis. 2007; 10(2):167-74 [PubMed] Related Publications
Progression to androgen independent (AI) is the main cause of death in prostate cancer, and the mechanism is still unclear. By reviewing the expression profiles of 26 prostate cancer samples in a holistic view, we found a group of genes differentially expressed in AI compared with androgen-dependent groups (P-value<0.01, t-test). Focusing on apoptosis, proliferation, hormone and angiogenesis, we found a group of genes such as thioredoxin domain containing 5 , tumor necrosis factor receptor superfamily, member 10a , ribosomal protein S19 and Janus kinase 2 upregulated in AI prostate cancer, could play important roles in the transition from AD to AI and could be biomarkers of prognosis.

Gazda HT, Kho AT, Sanoudou D, et al.
Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia.
Stem Cells. 2006; 24(9):2034-44 [PubMed] Free Access to Full Article Related Publications
Diamond-Blackfan anemia (DBA) is a broad developmental disease characterized by anemia, bone marrow (BM) erythroblastopenia, and an increased incidence of malignancy. Mutations in ribosomal protein gene S19 (RPS19) are found in approximately 25% of DBA patients; however, the role of RPS19 in the pathogenesis of DBA remains unknown. Using global gene expression analysis, we compared highly purified multipotential, erythroid, and myeloid BM progenitors from RPS19 mutated and control individuals. We found several ribosomal protein genes downregulated in all DBA progenitors. Apoptosis genes, such as TNFRSF10B and FAS, transcriptional control genes, including the erythropoietic transcription factor MYB (encoding c-myb), and translational genes were greatly dysregulated, mostly in diseased erythroid cells. Cancer-related genes, including RAS family oncogenes and tumor suppressor genes, were significantly dysregulated in all diseased progenitors. In addition, our results provide evidence that RPS19 mutations lead to codownregulation of multiple ribosomal protein genes, as well as downregulation of genes involved in translation in DBA cells. In conclusion, the altered expression of cancer-related genes suggests a molecular basis for malignancy in DBA. Downregulation of c-myb expression, which causes complete failure of fetal liver erythropoiesis in knockout mice, suggests a link between RPS19 mutations and reduced erythropoiesis in DBA.

Sengpiel V, Rost T, Görögh T, et al.
S19-mRNA expression in squamous cell carcinomas of the upper aerodigestive tract.
Anticancer Res. 2004 Jul-Aug; 24(4):2161-7 [PubMed] Related Publications
BACKGROUND: The differential display method showed altered expression of ribosomal protein S19 gene in human head and neck squamous cell carcinoma (HNSCC) cell lines.
MATERIALS AND METHODS: To verify these results, RT-PCR analysis was carried out in 18 HNSCC and 17 benign epithelial cell lines as well as 30 HNSCC and 8 reference tissue samples. In the HNSCC cells S19 mRNA expression was significantly reduced as compared to benign epithelial cells.
RESULTS: Change of the S19 gene expression in surgical samples was detectable but not significant although the histopathological grading of the HNSCC biopsies correlated significantly with the S19 mRNA expression levels. The expression of ribosomal protein S6 and S14 genes were additionally analyzed using the same methods.
CONCLUSION: High correlation was found between the expression of S6/S14 and S19 suggesting that changes in S19 gene expression might be the result of loss of ribosomes in HNSCC cells.

Li B, Sun M, He B, et al.
Identification of differentially expressed genes in human uterine leiomyomas using differential display.
Cell Res. 2002; 12(1):39-45 [PubMed] Related Publications
UNLABELLED: In searching of differentially expressed genes in human uterine leiomyomas, differential display was used with twelve pairs of primers to compare human uterine leiomyomas with matched myometrium. False positives were eliminated by reverse Northern analysis. Positives were confirmed by Northern blot analysis.
RESULTS: Four of 69 cDNA fragments (3 up-regulated named L1, L2 and L3 and 1 down-regulated named M1 in leiomyoma) were confirmed by Northern analysis. Sequence comparison and Northern analysis proved that L1 is exactly the human ribosomal protein S19. It was present ubiquitously in 13 tissues tested but in various levels and even in different size. L1 was highly expressed in parotidean cystadenocarcinoma, pancreatic cancer and breast cancer examined. No mutations have been found in human uterine leiomyomas (n=6).
CONCLUSIONS: hRPS19 overexpression might be a universal signal in rapid cell growth tissues.

Nishimura T, Horino K, Nishiura H, et al.
Apoptotic cells of an epithelial cell line, AsPC-1, release monocyte chemotactic S19 ribosomal protein dimer.
J Biochem. 2001; 129(3):445-54 [PubMed] Related Publications
A pancreatic carcinoma cell line, AsPC-1, underwent apoptosis in vitro when heat-treated for 60 min at 43 degrees C. Apoptotic AsPC-1 cells liberated a monocyte chemotactic factor into the culture supernatant 24 to 30 h after the heat-treatment. This factor was immunologically identified as the cross-linked homodimer of S19 ribosomal protein (RP S19), since the majority of the chemotactic activity was absorbed by both anti--RP S19 rabbit antibodies and an anti--isopeptide bond monoclonal antibody immobilized on agarose beads. Intracellular transglutaminase activity increased during the apoptotic process, reaching the peak strength between 18 and 24 h after the heat-treatment. A recombinant RP S19 acquired the monocyte chemotactic capacity when incubated with the apoptotic cell extract obtained at the 18th hour. The chemotactic activity acquirement as well as the transglutaminase activity were blocked by treatment of the extract with anti--type II transglutaminase rabbit antibodies. When the recombinant RP S19 was treated with an authentic type II transglutaminase, the dimerization of RP S19 concomitant with the generation of the monocyte chemotactic activity was observed. Peptide-map analyses involving amino acid sequencing demonstrated that the inter-molecular isopeptide bond was heterogeneous: Gln12 or Gln137 and Lys29 or Lys122 were cross-linked. Site-directed mutagenic analysis indicated that the cross-linking of Gln137, but not other residues such as Gln12, Lys29, and Lys122, was essential for expression of the chemotactic activity.

Shim C, Zhang W, Rhee CH, Lee JH
Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array.
Clin Cancer Res. 1998; 4(12):3045-50 [PubMed] Related Publications
The profiling of differentially expressed genes from primary tumor samples using cDNA expression array can reveal new tumor markers as well as target genes for therapeutic intervention. Using cDNA expression array technology, we produced an expression profile of genes that are associated with human cervical cancer. Hybridization of the cDNA blotting membrane (588 genes on a single membrane) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either normal cervix or cervical cancer. Parallel analyses of the hybridized signals enabled us to profile genes that were differentially expressed in cervical cancer. In each experiment, the extent of hybridization of each gene was evaluated by comparison with the most abundant mRNAs in the human cervix. These include myc proto-oncogene, 40S ribosomal protein S19, heat shock proteins, leukosialin S (CD43), integrin alphaL (CD11A), calgranulin (A), and CDK4 inhibitor (p16ink4). No detectable changes were observed in the expression levels of these genes. Several mRNAs, such as those encoding guanine nucleotide-binding protein Gs (alpha subunit), leukocyte adhesion protein (LFA1-beta), nuclear factor NF45, homeobox protein Hox-A1, and beta-catenin were detected in increased levels in cervical cancer. Genes that showed decreased expression in cervical cancer tissue were a group of apoptosis-related proteins, cell adhesion molecules, nuclear transcription factors, and a homeobox protein (Hox7). For example, the expression levels of Smad1 and Hox7 were consistently decreased in all tumor tissues tested. Northern analysis of Smad1 and Hox7 RNA in primary cervical tumor tissues and cervical carcinoma cell lines indicated that, in general, the mRNA levels of these genes were decreased in human cervical cancer. The precise relationship between the altered expression of these genes and cervical tumorigenesis is a matter of further investigation.

Kondoh N, Schweinfest CW, Henderson KW, Papas TS
Differential expression of S19 ribosomal protein, laminin-binding protein, and human lymphocyte antigen class I messenger RNAs associated with colon carcinoma progression and differentiation.
Cancer Res. 1992; 52(4):791-6 [PubMed] Related Publications
Three complementary DNA encoding S19 ribosomal protein (S19), laminin-binding protein (LBP), and HLA class I (HLA-I) genes were isolated from a colon tumor-enriched subtraction library. To evaluate this mRNA expression, surgically removed colon tumors as well as matched normal tissue and human colon carcinoma cell lines showing various differentiation states, anchorage dependence, and proliferation states were examined by Northern blot analysis. The mRNA level of S19 mRNA (0.6 kilobase) was higher in primary colon carcinoma tissue than in matched normal colon tissue in 5 of 6 cases. In 2 of 4 cases, the expression of LBP mRNA (1.2 kilobases) was higher in carcinoma than in normal tissue. In 12 human colon cell lines, the level of LBP mRNA was higher in poorly differentiated cells. On the other hand, HLA-I mRNA (1.7 kilobases) was higher in well-differentiated cells. Although the S19 mRNA was expressed in both well- and poorly differentiated cells, a concomitant increase with tumor progression was observed in two pairs of cell lines derived from the same patients (SW480 and SW620; COLO201 and COLO205). Anchorage dependence of butyrate-treated HT29 colon carcinoma cells was correlated with lower levels of S19 and LBP mRNAs and higher levels of HLA-I mRNA expression compared with untreated cells. While the expression of S19 and LBP mRNAs was not changed due to cell growth states, HLA-I mRNA levels were found to be low in proliferating HT29 cells but highly induced in contact-inhibited cells. In summary, therefore, high expression of S19 and LBP combined with low expression of HLA-I were well correlated with colon carcinoma cells of higher malignant potential.

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Cite this page: Cotterill SJ. RPS19, Cancer Genetics Web: http://www.cancer-genetics.org/RPS19.htm Accessed:

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