Previously we have identified the rplA gene encoding ribosomal protein L1 in Streptomyces aureofaciens. Sequence comparison of ribosomal protein L1 among several bacterial genera revealed a high level of conservation. Based on this conservation, these proteins were used as a phylogenetic tool to compare evolutionary relationships among eubacteria and archaebacteria. This phylogenetic analysis of L1 ribosomal proteins including the S. aureofaciens rplA gene product revealed, except similar bacterial groupings, some new evolutionary relationships.

• MeSH
• Archaea klasifikace   genetika   MeSH
• Bacteria klasifikace   genetika   MeSH
• bakteriální geny MeSH
• bakteriální proteiny klasifikace   genetika   MeSH
• fylogeneze MeSH
• molekulární sekvence - údaje MeSH
• ribozomální proteiny klasifikace   genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• Streptomyces aureofaciens klasifikace   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• ribosomal protein L1 MeSH Prohlížeč
• ribozomální proteiny MeSH

Diamond-Blackfan anemia (DBA) is a congenital red blood cell aplasia that is usually diagnosed during early infancy. Apart from defects in red blood cell maturation, the disorder is also associated with various physical anomalies in 40% of patients. Mutations in the ribosomal protein (RP) S19 are found in 25% of patients, while mutations in other proteins of the small ribosomal subunit--RPS17 and RPS24--have been found in a fraction of patients. Recently, mutations in RPL5, RPL11, and RPL35a of the large ribosomal subunit have also been reported in several DBA patients. Here, we present the identification of mutations in the RPL5 and RPL11 genes in patients from the Czech DBA Registry. Mutations in RPL5 were identified in eight patients from 6 out of 28 families (21.4%), and mutations in RPL11 in two patients from 2 out of 28 families (7.1%). Interestingly, all 10 patients with either an RPL5 or RPL11 mutation exhibited one or more physical anomalies; specifically, thumb anomalies (flat thenar) were always present, while no such anomaly was observed in seven patients with an RPS19 mutation. Moreover, 9 out of 10 patients with either an RPL5 or RPL11 mutation were born small for gestational age (SGA) compared to 3 out of 7 patients from the RPS19-mutated group. These observations may suggest that mutations, at least in RPL5, seem to generally have more profound impact on fetal development than mutations in RPS19. Since RPL5 and RPL11, together with RPL23, are also involved in the MDM2-mediated p53 pathway regulation, we also screened the RPL23 gene for mutations; however, no mutations were identified.

• MeSH
• Diamondova-Blackfanova anemie genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• frekvence genu MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• registrace MeSH
• ribozomální proteiny genetika   MeSH
• sekvence nukleotidů MeSH
• senioři MeSH
• zdraví rodiny MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• ribosomal protein L11 MeSH Prohlížeč
• ribosomal protein L5 MeSH Prohlížeč
• ribozomální proteiny MeSH

Phosphorylation of ribosomal acidic proteins of Saccharomyces cerevisiae is an important mechanism regulating a number of active ribosomes. The key role in the regulatory mechanism is played by specific phosphoprotein kinases and phosphoprotein phosphatases. Three different cAMP-independent protein kinases phosphorylating acidic ribosomal proteins have been identified and characterized. The protein kinase 60S (PK60S), RAP kinase, and casein kinase type 2 (CK2). All three protein kinases phosphorylate serine residues which are localized in the C-terminal end of phosphoproteins. Synthetic peptides were used to determinate the amino acid sequence of phosphoacceptor site for PK60S. Peptide AAEESDDD derived from phosphoproteins YP1 beta/beta' and YP2 alpha turned out to be the best substrate for PK60S. A number of halogenated benzimidazoles and 2-azabenzimidazoles were tested as inhibitors of the three protein kinases. 4,5,6,7-Tetrabromo-2-azabenzimidazole inhibits phosphorylation only of these polypeptides phosphorylated by protein kinase 60S, namely YP1 beta/beta' and YP2 alpha, but not the other, YP1 alpha and YP2 beta phosphorylated by protein kinases RAP and CK2. RAP kinase has been found in an active form in the soluble fraction of S. cerevisiae. The enzyme uses ATP as a phosphate donor and is less sensitive to heparin than casein kinase 2. RAP kinase monophosphorylates the four acidic proteins. The ribosome-bound proteins are a better substrate for the enzyme. Multifunctional CK2 kinase phosphorylate all four acidic proteins. The kinase phosphorylates preferentially serine or threonine residues surrounded by cluster of acidic residues. The enzyme activity is stimulated in vitro by the presence of polylysine and inhibited by heparin.

• MeSH
• fosforylace MeSH
• fungální proteiny metabolismus   MeSH
• kaseinkinasa II MeSH
• protein-serin-threoninkinasy metabolismus   MeSH
• proteinkinasy metabolismus   MeSH
• ribozomální proteiny metabolismus   MeSH
• Saccharomyces cerevisiae enzymologie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• 60S ribosomal protein kinase MeSH Prohlížeč
• fungální proteiny MeSH
• kaseinkinasa II MeSH
• protein-serin-threoninkinasy MeSH
• proteinkinasy MeSH
• RAP kinase MeSH Prohlížeč
• ribozomální proteiny MeSH

Genes encoding the KDM5 family of transcriptional regulators are disrupted in individuals with intellectual disability (ID). To understand the link between KDM5 and ID, we characterized five Drosophila strains harboring missense alleles analogous to those observed in patients. These alleles disrupted neuroanatomical development, cognition and other behaviors, and displayed a transcriptional signature characterized by the downregulation of many ribosomal protein genes. A similar transcriptional profile was observed in KDM5C knockout iPSC-induced human glutamatergic neurons, suggesting an evolutionarily conserved role for KDM5 proteins in regulating this class of gene. In Drosophila, reducing KDM5 changed neuronal ribosome composition, lowered the translation efficiency of mRNAs required for mitochondrial function, and altered mitochondrial metabolism. These data highlight the cellular consequences of altered KDM5-regulated transcriptional programs that could contribute to cognitive and behavioral phenotypes. Moreover, they suggest that KDM5 may be part of a broader network of proteins that influence cognition by regulating protein synthesis.

• MeSH
• aktivace transkripce MeSH
• Drosophila melanogaster genetika   metabolismus   MeSH
• Drosophila genetika   metabolismus   MeSH
• histondemethylasy metabolismus   genetika   MeSH
• lidé MeSH
• mentální retardace genetika   metabolismus   MeSH
• mitochondrie metabolismus   genetika   MeSH
• neurony * metabolismus   MeSH
• proteiny Drosophily * genetika   metabolismus   MeSH
• proteosyntéza MeSH
• ribozomální proteiny * genetika   metabolismus   MeSH
• ribozomy metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histondemethylasy MeSH
• KDM5C protein, human MeSH Prohlížeč
• Lid protein, Drosophila MeSH Prohlížeč
• proteiny Drosophily * MeSH
• ribozomální proteiny * MeSH

Protein kinase activity associated with ribosomes of a kirromycin-producing strain of Streptomyces collinus was detected. The enzyme utilizes [gamma-32P]ATP to phosphorylate proteins, yielding acid-stable phosphoamino acids. Two-dimensional electrophoresis of proteins from a crude ribosomal fraction revealed 17 phosphoproteins. Eleven of the phosphoproteins exhibited electrophoretic mobility identical to that of S. collinus ribosomal proteins S3, S4, S12, S13, S14, S18, L2, L7, L16, L17, and L23. Protein L2 was identified by microsequencing of internal peptide fragments. Immunodetection with monoclonal antibodies indicated that the ribosomal proteins are phosphorylated on serine and threonine residues. Phosphorylation of ribosomal proteins led to the reduction of activity of ribosomes in the translation of poly(U). These results provide the first evidence of phosphorylation of ribosomal proteins in bacteriophage-uninfected cells of eubacteria.

• MeSH
• 2D gelová elektroforéza MeSH
• bakteriální proteiny metabolismus   MeSH
• fosforylace MeSH
• proteinkinasy metabolismus   MeSH
• ribozomální proteiny metabolismus   MeSH
• ribozomy metabolismus   MeSH
• Streptomyces metabolismus   ultrastruktura   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• proteinkinasy MeSH
• ribozomální proteiny MeSH

Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell hypoplasia characterized by a selective defect of erythropoiesis with a normochromic macrocytic anemia and reticulocytopenia often accompanied by various congenital anomalies. The critical region responsible for the pathogenesis of DBA has been mapped in some patients to chromosome 19q13.2 (P Gustavsson, E Garelli, N Draptchinskaia, et al. Am. J. Hum. Genet. 63:1388-1395, 1998) and the gene encoding ribosomal protein S19 (RPS19) is believed to be the candidate gene. Here we present molecular analysis of the RPS19 gene in DBA patients from the Czech National DBA Registry. We found that the RPS19 gene was mutated in 25% (5/20) of DBA patients (insertion, deletion, and point mutations, but no nonsense or splice site mutations). Point mutations were localized to hot spots defined by Willig (TN Willig, N Draptchinskaia, I Dianzani, et al. Blood 94:4294-4306, 1999). Moreover, we describe two processed RPS19 pseudogenes, which were not expressed. Possible models of the DBA pathogenesis in the view of RPS19 mutations are discussed.

• MeSH
• dítě MeSH
• dospělí MeSH
• Fanconiho anemie etiologie   genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• molekulární sekvence - údaje MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• pseudogeny * MeSH
• ribozomální proteiny genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ribosomal protein S19 MeSH Prohlížeč
• ribozomální proteiny MeSH

Ribosome biogenesis is a highly dynamic, steady-state nucleolar process that involves synthesis and maturation of rRNA, its transient interactions with non-ribosomal proteins and RNPs and assembly with ribosomal proteins. In the few years of the 21st century, an exciting progress in the molecular understanding of rRNA and ribosome biogenesis has taken place. In this review, we discuss the recent results on the regulation of rRNA synthesis in relation to the functional organization of the nucleolus, and put an emphasis on the situation encountered in mammalian somatic cells.

• MeSH
• biologické modely MeSH
• buněčné jadérko genetika   fyziologie   ultrastruktura   MeSH
• buněčný cyklus genetika   fyziologie   MeSH
• chromatin fyziologie   ultrastruktura   MeSH
• genetická transkripce genetika   MeSH
• lidé MeSH
• proliferace buněk MeSH
• regulace genové exprese MeSH
• ribozomální DNA genetika   MeSH
• RNA ribozomální genetika   MeSH
• RNA-polymerasa I metabolismus   MeSH
• transmisní elektronová mikroskopie MeSH
• umlčování genů fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• chromatin MeSH
• ribozomální DNA MeSH
• RNA ribozomální MeSH
• RNA-polymerasa I MeSH

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia characterized as a normochromic macrocytic anemia with a selective deficiency in red blood cell precursors in otherwise normocellular bone marrow. In 40% of DBA patients, various physical anomalies are also present. Currently two genes are associated with the DBA phenotype--the ribosomal protein (RP) S19 mutated in 25% of DBA patients and RPS24 mutated in approximately 1.4% of DBA patients. Here we report the identification of a mutation in yet another ribosomal protein, RPS17. The mutation affects the translation initiation start codon, changing T to G (c.2T>G), thus eliminating the natural start of RPS17 protein biosynthesis. RNA analysis revealed that the mutated allele was expressed, and the next downstream start codon located at position +158 should give rise to a short peptide of only four amino acids (Met-Ser-Arg-Ile). The mutation arose de novo, since all healthy family members carry the wild-type alleles. The identification of a mutation in the third RP of the small ribosomal subunit in DBA patients further supports the theory that impaired translation may be the main cause of DBA pathogenesis.

• MeSH
• Diamondova-Blackfanova anemie genetika   MeSH
• dospělí MeSH
• kodon iniciační MeSH
• lidé MeSH
• malé podjednotky ribozomu genetika   MeSH
• mutace * MeSH
• ribozomální proteiny genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kodon iniciační MeSH
• ribosomal protein S17 MeSH Prohlížeč
• ribozomální proteiny MeSH

Azacitidine (AZA) is a hypomethylating drug used to treat disorders associated with myelodysplasia and related neoplasms. Approximately 50 % of patients do not respond to AZA and have very poor outcomes. There is thus great interest in identifying predictive biomarkers for AZA responsiveness. We searched for specific genes whose expression level was associated with response status. Using microarrays, we analyzed gene expression patterns in bone marrow CD34+ cells in serial samples from 32 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes before and during the AZA therapy. At baseline, a comparison of the responders and non-responders showed 52 differentially expressed genes (P < 0.01). Functional annotation of the deregulated genes revealed categories primarily related to ribosomes and pathways associated with proliferation. The expression level of RPL28 correlated with overall survival. We identified altered expression in 167 genes in responders, 26 genes in non-responders with stable disease, and 13 genes in non-responders with disease progression using paired t test of expression levels in patients before and during treatment. Our data indicate that AZA treatment failure is associated with the up-regulation of ribosomal genes/pathways that are likely related to intensive proteosynthesis in proliferative/neoplastic cells of non-responders.

• Klíčová slova
• Azacitidine, Gene expression profiling, Myelodysplastic syndromes, Ribosomal genes,
• MeSH
• akutní myeloidní leukemie genetika   MeSH
• azacytidin farmakologie   terapeutické užití   MeSH
• buňky kostní dřeně metabolismus   MeSH
• chronická myelomonocytární leukemie genetika   MeSH
• lidé MeSH
• myelodysplastické syndromy farmakoterapie   genetika   MeSH
• neúspěšná terapie MeSH
• proliferace buněk genetika   MeSH
• ribozomální proteiny genetika   MeSH
• transkriptom účinky léků   MeSH
• upregulace účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azacytidin MeSH
• ribozomální proteiny MeSH

DNA repair events have functional significance especially for genome stability. Although the DNA damage response within the whole genome has been extensively studied, the region-specific characteristics of nuclear sub-compartments such as the nucleolus or fragile sites have not been fully elucidated. Here, we show that the heterochromatin protein HP1 and PML protein recognize spontaneously occurring 53BP1- or γ-H2AX-positive DNA lesions throughout the genome. Moreover, 53BP1 nuclear bodies, which co-localize with PML bodies, also occur within the nucleoli compartments. Irradiation of the human osteosarcoma cell line U2OS with γ-rays increases the degree of co-localization between 53BP1 and PML bodies throughout the genome; however, the 53BP1 protein is less abundant in chromatin of ribosomal genes and fragile sites (FRA3B and FRA16D) in γ-irradiated cells. Most epigenomic marks on ribosomal genes and fragile sites are relatively stable in both non-irradiated and γ-irradiated cells. However, H3K4me2, H3K9me3, H3K27me3 and H3K79me1 were significantly changed in promoter and coding regions of ribosomal genes after exposure of cells to γ-rays. In fragile sites, γ-irradiation induces a decrease in H3K4me3, changes the levels of HP1β, and modifies the levels of H3K9 acetylation, while the level of H3K9me3 was relatively stable. In these studies, we confirm a specific DNA-damage response that differs between the ribosomal genes and fragile sites, which indicates the region-specificity of DNA repair.

• MeSH
• 53BP1 MeSH
• chromatin genetika   MeSH
• chromozomální proteiny, nehistonové metabolismus   účinky záření   MeSH
• DNA vazebné proteiny účinky záření   MeSH
• fibroblasty účinky záření   MeSH
• fragilní místa na chromozomu genetika   MeSH
• histony účinky záření   MeSH
• homolog proteinu s chromoboxem 5 MeSH
• jaderné proteiny metabolismus   účinky záření   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny metabolismus   účinky záření   MeSH
• nestabilita genomu MeSH
• oprava DNA genetika   MeSH
• osteosarkom MeSH
• poškození DNA účinky záření   MeSH
• protein promyelocytické leukemie MeSH
• ribozomy genetika   MeSH
• transkripční faktory metabolismus   účinky záření   MeSH
• záření gama MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 53BP1 MeSH
• CBX1 protein, human MeSH Prohlížeč
• chromatin MeSH
• chromozomální proteiny, nehistonové MeSH
• DNA vazebné proteiny MeSH
• histony MeSH
• homolog proteinu s chromoboxem 5 MeSH
• jaderné proteiny MeSH
• nádorové supresorové proteiny MeSH
• Pml protein, mouse MeSH Prohlížeč
• protein promyelocytické leukemie MeSH
• transkripční faktory MeSH
• Trp53bp1 protein, mouse MeSH Prohlížeč