Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genes, rel”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1975

Quinone induced stringent control. Accumulation of ppGpp and inhibition of RNA synthesis in stringent Escherichia coli by 5,8-dioxo-6-amino-7-chloroquinoline.

The mode of action of a synthetic cytostatic quinone was studied in Escherichia coli. 1. At concentrations of 1.5-6 mug/ml, 5,8-dioxo-6-amino-7-chloroquinoline rapidly inhibits growth and protein synthesis in E. coli. The synthesis of RNA is immediately affected in E. coli rel+ whereas in E. coli rel- the accumulation of RNA can proceed on addition of the quinone. This indicates that the inhibition of RNA synthesis in the stringent strain is a consequence of the regulatory phenomenon governed by the rel gene. 2. Chloramphenicol, known to abolish the stringent control mechanism, added simultaneously with the quinone allows the accumulation of RNA to proceed in the stringent strain. 3. Guanosine tetraphosphate accumulates in quinone-treated E. coli rel+ but not in the relaxed mutant strain. 4. Addition of amino acids reverses all inhibitory effects observed in quinone treated stringent and relaxed cells. 5. It is concluded that the bacteriostatic effect of 5,8-dioxo-6-amino-7-chloroquinoline on E. coli is caused by an apparent intracellular amino acid starvation.

Alanine↗
PubMed2004

Divergent C-terminal transactivation domains of Rel/NF-kappa B proteins are critical determinants of their oncogenic potential in lymphocytes.

rel/nf-kappaB genes are amplified, overexpressed, or constitutively activated in many human hematopoietic tumors; however, the molecular mechanisms by which they contribute to tumorigenesis remain to be determined. Here, we explored the oncogenic potential of cellular Rel/NF-kappaB proteins in vitro and in vivo. We show that overexpression of wild-type mouse and human c-rel genes suffices to malignantly transform primary spleen cells in stringent soft agar assays and produce fatal tumors in vivo. In contrast relA and a constitutively active form of IKKbeta did not. Importantly, a hybrid RelA protein with its C-terminal transactivation domain substituted by that of v-Rel was potently oncogenic in vitro and in vivo. The transactivation domain of v-Rel selectively conferred an oncogenic phenotype upon the Rel homology domain (RHD) of RelA, but not to the more divergent RHDs of p50/NF-kappaB1, p52/NF-kappaB2, or RelB. Collectively, our results highlight important differences in the intrinsic oncogenic activity of mammalian c-Rel and RelA proteins, and indicate that critical determinants of their differential oncogenicity reside in their divergent transactivation domains. These findings provide experimental evidence for a role of mammalian Rel/NF-kappaB factors in leukemia/lymphomagenesis in an in vivo animal model, and are consistent with the implication of c-rel in many human lymphomas.

Adenoviridae↗
PubMed1979

Regulatory nucleotides involved in the Rel function of Bacillus subtilis.

We have examined the accumulation of polyphosphorylated nucleotides in Bacillus subtilis in relation to the function of the rel gene. Our results are as follows. (i) During inhibition of isoleucine activation by O-methylthreonine, wildtype B. subtilis cells accumulate unusual nucleotides with the chromatographic and chemical properties of pppApp, ppApp, pppGpp, ppGpp, pGpp, and ppGp. (ii) During the carbon source downshift elicited by inhibiting glucose uptake, we observed accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iii) At the end of long phase in sporulation medium, we observed a small transient accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iv) We were unable to detect a nucleotide with chromatographic behavior expected for pppAppp under any conditions. (v) The rel mutant of Swanton and Edlin (Biochem. Biophys. Res. Commun. 46-583-588, 1972) did not accumulate any of these polyphosphorylated nucleotides under any of the conditions examined. (vi) the rel mutant is unimpaired in sporulation. We conclude that one or more of the nucleotides we have detected may be involved in controlling the specificity of transcription during the stringent response, but none of them are required for sporogenesis.

Adenine Nucleotides↗
PubMed1996

Cloning and transcription factor-binding sites of the human c-rel proto-oncogene promoter.

We report here the cloning, sequencing, functional analysis and DNase I footprinting of the human c-rel promoter region. The results revealed an 824-bp BsaAI-StuI minimal promoter region with a large number of NF-kappa B, Ap2 and Sp1-binding sites, some of them variants of known consensus sequences. This is the first promoter in the Rel/NF-kappa B/I kappa B family to be subjected to a detailed footprinting analysis for the binding of transcription activator proteins. Our finding of 14 Ap2-binding sites may indicate why the human c-rel promoter, unlike the chicken c-rel promoter, has a strong function and is highly responsive to phorbol esters. The presence of five NF-kappa B and six Sp1-binding sites in turn adds to growing evidence that, in mammals, the promoter of the Rel/NF-kappa B/I kappa B family may utilize multiple NF-kappa B- and Sp1-binding sites for their interactive regulation. Furthermore, there are putative binding sites for the PU.1 and Oct 1/2 transcription activator proteins, also present in the mouse c-rel promoter, which may help explain the preferential transcription of the c-rel gene in B- and T-lymphoid cells.

Amino Acid Sequence↗
PubMed1972

Control of nucleotide metabolism and ribosomal ribonucleic acid synthesis during nitrogen starvation of Escherichia coli.

Ribosomal ribonucleic acid (RNA) synthesis and ribonucleoside triphosphate metabolism were studied in cultures of Escherichia coli subjected to starvation for inorganic nitrogen. In a strain that was under stringent control, a 50-fold reduction in the formation of both 16S and 23S RNA was accompanied by a severe restriction on nucleotide biosynthesis. These inhibitions were relieved in part by incubating the starved cells with amino acids. This result suggests that regulation by the functional RNA control (RC) gene is involved in the effect. This suggestion was confirmed by showing that the effector of the stringent response, guanosine-5'-diphosphate-2'- or 3'-diphosphate ((pp)G(pp)), accumulated at the onset of starvation and disappeared immediately when the amino acids were added. Ribosomal RNA synthesis was severely restricted and the same nucleotide, (pp)G(pp), accumulated at the onset of nitrogen starvation of a relaxed mutant too. These findings suggest that a control mechanism other than the one provided by the functional rel gene might operate to regulate RNA synthesis and that this mechanism is expressed through the synthesis of (pp)G(pp).

Amino Acids↗
PubMed1993

Lipopolysaccharide stimulates both nuclear localization of the nuclear factor kappa B 50-kDa subunit and loss of the 105-kDa precursor in RAW264 macrophage-like cells.

Nuclear factor kappa B (NF-kappa B) is an important regulator of gene expression in cells of the immune system. One such gene, tumor necrosis factor, is induced by bacterial lipopolysaccharide (LPS) in macrophages, and this induction has been shown to be mediated in part by NF-kappa B activation in murine macrophages. In this study, immunochemical analysis was used to follow LPS activation of the NF-kappa B 50-kDa subunit in the RAW264 macrophage-like cell line. The recombinant NF-kappa B 50-kDa subunit was used as an immunogen to produce a rabbit antiserum, which was then affinity-purified using a portion of the NF-kappa B 50-kDa subunit that does not have homology to other members of the c-rel gene family. Untreated macrophages had little NF-kappa B in the nucleus as detected by Western immunoblotting. The protein was predominantly localized in the cytoplasmic fraction. Interestingly, NF-kappa B was found as the 50-kDa mature protein and 105-kDa precursor. After LPS treatment, there was a rapid nuclear translocation of NF-kappa B as detected by immunoblot analysis. There was also a rapid decrease in the amount of the cytoplasmic 105-kDa protein. This may indicate that the 105-kDa protein is a reservoir for the 50-kDa protein and that one of the actions of LPS is to increase the rate of 105-kDa precursor processing.

Animals↗
PubMed2002

Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma.

To address the possible genetic relationship between primary mediastinal large-B-cell lymphoma (PMLBCL) and diffuse large-B-cell lymphoma (DLBCL), we compared DNA copy number changes identified by comparative genomic hybridization (CGH) analysis of 40 PMLBCL and 91 DLBCL tumors. We assessed their karyotypes by G-banding; amplification of MYC, BCL2, and REL genes by Southern blotting; and incidence of nonpolymorphic BCL6 mutations by single-strand conformation polymorphism analysis (SSCP). Overall, CGH identified overlapping and nonoverlapping patterns of DNA copy number changes in the two groups. Among the latter changes, gains of chromosomes 8, 11, 15, and 16 and losses of chromosomes 5, 10, 15, 16, 17, and 20 were seen only in DLBCL, and gains of chromosomes 10, 21, and 22 and losses of chromosomes 11, 13, and 18 were seen only in PMLBCL. Several overlapping changes were identified in both groups, with variation in incidence. Statistical analysis of these changes showed significant gains of chromosomes 3 (P <or= 0.05) and 7q (P <or= 0.05) in DLBCL and gains of chromosomes 9 (P <or= 0.05) and 19 (P <or= 0.05) and the X chromosome (P <or= 0.05) and loss of chromosome 4 (P <or= 0.05) in PMLBCL. Frequent recurring DNA amplification at 2p13-15 and less frequent amplification at 6p21, 12q13, and 18q21 were noted in both groups. Recurring amplification at 1q21 was seen only in DLBCL, whereas nonrecurring amplification at 10p11.2 and 15q22-24 was seen only in PMLBCL. G-banded karyotype analysis identified t(3;14)(q27;q32) in one and t(14;18)(q32;q21) in two cases of PMLBCL. Seven of 13 cases exhibited SSCP variants in the 5' noncoding region of BCL6. In addition, 19 of 24 PMLBCLs assayed for BCL6 protein expression by immunohistochemistry showed positive results, indicating an origin from a germinal center (GC)-derived B cell. Based on these data, we conclude that PMLBCL is a distinct entity among GC-derived high-grade DLBCLs.

Adolescent↗
PubMed1977

On the control of ribosomal protein biosynthesis in Escherichia coli. I. Studies on ribosomal protein biosynthesis in amino acid-starved cells.

The rate of individual ribosomal protein synthesis relative to total protein synthesis has been determined in Escherichia coli rel+ and rel- cells, under valyltRNA deprivation. These strains have a temperature-sensitive valyl-tRNA synthetase. Starvation was obtained following transfer to the cells to non-permissive temperature. Ribosomal proteins were obtained by treatment of either total lysates of freeze-thawed lysozyme spheroplasts or ammonium sulphate precipitate of ribosomes, with acetic acid. Differential labelling of the ribosomal proteins was observed in both strains: proteins from the rel+ strain appear more labelled than those from the rel- strain, the rate of labelling of individual proteins being about the same in both strains. Moreover ribosomal proteins were found as stable during starvation as total protein. It is thus concluded that in starving cells individual ribosomal proteins are not synthesized at equal rates. This indicates that the synthesis of ribosomal proteins is not only under the control of the rel gene.

Amino Acids↗
PubMed1996

Negative regulation of dorsal patterning in early embryos by overexpression of XrelA, a Xenopus homologue of NF-kappa B.

Recent results by Richardson et al. (Mech. Dev., 52 (1995) 165-177) suggest that the Xenopus Rel gene XrelA may be involved in the formation of the head and tail of the early embryo. We present evidence to suggest that wild-type XrelA also has a role in dorsoventral development. XrelA overexpression in the dorsal side of embryos reduces dorsal development and attenuates in vitro dorsal morphogenetic movements. XrelA also strongly reduces axis duplication caused by overexpression of a dominant negative mutant of Xenopus glycogen synthase kinase-3 beta. Our results indicate that XrelA may have a role in dorsoventral patterning in early embryos.

Age Factors↗
PubMed1991

Generation of p50 subunit of NF-kappa B by processing of p105 through an ATP-dependent pathway.

The transcription factor NF-kappa B is a heterodimer consisting of two proteins encoded by different members of the rel gene family (p50 and p65). The p50 subunit is unusual among DNA-binding proteins in that its functional form is encoded in an open reading frame of relative molecular mass 105,000 (p105; ref. 4). The N-terminal region of this open reading frame encodes p50, whereas the remaining C terminus contains ankyrin repeats. Although p50 binds to DNA, full-length p105 translated in vitro does not. The mechanism by which p50 is generated in vivo, and the fate of the C-terminal region of p105 have not been established. Here we show that functional p50 is produced by ATP-dependent proteolysis of p105. Moreover, we find that the C-terminal half of p105 is not required for processing in vivo, and is rapidly degraded on processing. We propose that the C-terminal region of p105 is involved in the cytoplasmic assembly of the complex between the p50/p65 heterodimer and the inhibitor I kappa B.

Adenosine Triphosphate↗
PubMed2001

Evidence for local immunosuppression and demonstration of c-myc amplification in pyothorax-associated lymphoma.

AIMS: Pyothorax-associated lymphoma (PAL) develops in the pleural cavity of patients with a long history of pyothorax. Epstein-Barr virus (EBV) is also involved in PAL, similar to lymphomas in immunodeficient patients. Here we examined T-lymphocyte subsets as well as c-myc and REL gene amplification in PAL tissues. METHODS AND RESULTS: We determined the number and distribution of CD4+ and CD8+ T-lymphocytes, to evaluate T-cells in the host immune reaction in seven cases of PAL. As controls, we also studied 10 cases of extranodal diffuse large B-cell lymphoma (DLBL) and 10 cases of nodal DLBL. Chromosomal imbalances in PAL were determined by using comparative genomic hybridization (CGH) analysis. The mean numbers of CD4+ and CD8+ and their ratio were significantly lower in PAL than in nodal DLBL. CGH analysis of PAL showed amplification of the 8q24 chromosomal region. In addition, c-myc amplification was found in four cases of PAL by Southern blot analysis. CONCLUSIONS: Our results suggest that the development of PAL may involve a local immunosuppressive environment and that amplification of c-myc might promote tumour progression, as has been described in the development of Burkitt's lymphoma.

Aged↗
PubMed1973

Synthesis of guanosine tetra- and pentaphosphate requires the presence of a codon-specific, uncharged transfer ribonucleic acid in the acceptor site of ribosomes.

The nucleotides ppGpp and pppGpp accumulate when wild-type, but not rel(-), strains of Escherichia coli are starved for required amino acids. These compounds are synthesized on ribosomes, in the presence of the product of the rel gene, from GDP and GTP; ATP is used as the phosphate donor. The signal for making these compounds is the presence of an uncharged tRNA in the ribosomal acceptor site. These compounds are not accumulated if the ribosomes are actively engaged in protein synthesis.

Adenosine Triphosphate↗
PubMed1975

Studies on the control of development. Accumulation of guanosine tetraphosphate and pentaphosphate in response to inhibition of protein synthesis in Bacillus subtilis.

Bacillus subtilis cells accumulate unusual phosphorylated substances at the end of logarithmic growth in a semi-synthetic medium. Two of these substances are guanosine 3'(2')-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'(2')-diphosphate 5'-triohosphate (pppGpp) which, in contrast to amino-acid-starved Escherichia coli cells, are not degraded in sporulating cells of B. subtilis after the addition of chloramphenicol. Moreover, inhibition of protein synthesis in growing cells of B. subtilis causes accumulation of ppGpp and pppGpp, which is also in contrast to E. coli. This was shown by isolation and characterization of substances produced in these cells after the addition of chloramphenicol. Other inhibitors of protein synthesis acting at the ribosomal level also cause the accumulation of ppGpp and pppGpp. There is no difference between the action of antibiotics affecting 50-S and/or 30-S ribosomal subunits, since chloramphenicol, tetracycline erythromycin and neomycin cause the accumulation of almost equal amounts of these nucleotides. This apparently resolves the close connection between ppGpp accumulation and the rate of stable RNA synthesis, which was believed to exist also in B. subtilis because of the stringent response observed after amino acid starvation coupled with ppGpp accumulation. Antibiotics which inhibit protein synthesis differently than by affecting the ribosomes (puromycin) or which inhibit RNA (rifampicin) or DNA (nalidixic acid) synthesis do not cause ppGpp accumulation. The accumulation of ppGpp and pppGpp in the presence of charged tRNA provided by chloramphenicol treatment suggests that the signal for the synthesis of unusual nucleotides is an inhibition of the binding of tRNA (charged or uncharged) to the acceptor site of the ribosome. This activates the rel gene product which forms ppGpp and pppGpp from GTP and ATP. Sporulating cells of B. subtilis without chloramphenicol treatment produce besides ppGpp and pppGpp other unusual substances, which are likely to be highly phosphorylated nucleotides contained adenine as base moiety.

Bacillus subtilis↗
PubMed1973

Role of the translocation factor G in the regulation of ribonucleic acid synthesis.

In an Escherichia coli rel(+)arg strain (ES-2) which carries a temperature-sensitive "G factor," the synthesis of ribonucleic acid (RNA) continues at the nonpermissive temperature (42 C) even though protein synthesis is terminated. However, at 32 C, the strain exhibits a stringent control of RNA synthesis in the absence of arginine. The stringent control of RNA synthesis imposed by trimethoprim (an inhibitor of initiation of protein synthesis) at 32 C is released at the nonpermissive temperature. Even the diauxie lag in RNA synthesis, which is regulated independently of the allelic state of the rel gene, is overcome by inactivation of the G factor. The unusual guanosine nucleotide, guanosine 5'-diphosphate 2' or 3'-diphosphate (ppGpp), is produced in small amounts during growth in strain ES-2. Withdrawal of arginine results in a greater accumulation of this compound at 32 C. At 42 C, the synthesis of ppGpp is abolished and is considerably lower than the level found in ES-2 under normal growth conditions. These results indicate that the translocation factor G plays an important role in the regulation of RNA synthesis and in the synthesis of ppGpp.

Arginine↗
PubMed1987

Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor.

I investigated the significance of the intracellular accumulation of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) and of the coordinated decrease in the GTP pool for initiating morphological and physiological differentiation of Streptomyces griseus, a streptomycin-producing strain. In solid cultures, aerial mycelium formation was severely suppressed by the presence of excess nutrients. However, decoyinine, a specific inhibitor of GMP synthetase, enabled the cells to develop aerial mycelia in the suppressed cultures at concentrations which only partially inhibited growth. A factor (2S-isocapryloyl-3S-hydroxymethyl-gamma-butyrolactone) added exogenously had no such effect. Decoyinine was also effective in initiating the formation of submerged spores in liquid culture. The ability to produce streptomycin did not increase but decreased drastically on the addition of decoyinine. This sharp decrease in streptomycin production was accompanied by a decrease in intracellular accumulation of ppGpp. A relaxed (rel) mutant was found among 25 thiopeptin-resistant isolates which developed spontaneously. The rel mutant had a severely reduced ability to accumulate ppGpp during a nutritional shift-down and also during postexponential growth and showed a less extensive decrease in the GTP pool than that in the rel+ parental strain. The rel mutant failed to induce the enzymes amidinotransferase and streptomycin kinase, which are essential for the biosynthesis of streptomycin. The abilities to form aerial mycelia and submerged spores were still retained, but the amounts were less, and for both the onset of development was markedly delayed. The decreased ability to produced submerged spores was largely restored by the addition of decoyinine. This was accompanied by an extensive GTP pool decrease. The rel mutant produced A factor normally, indicating that synthesis of A factor is controlled neither by ppGpp nor by GTP. Conversely, a mutant defective in A-factor synthesis accumulated as much ppGpp as did the parental strain. It was concluded that morphological differentiation of S. griseus results from a decrease in the pool of GTP, whereas physiological differentiation results from a more direct function of the rel gene product (ppGpp). It is also suggested that A factor may render the cell sensitive to receive and respond to the specified signal molecules, presumably ppGpp (for physiological differentiation) or GTP (for morphological differentiation).

4-Butyrolactone↗
PubMed2006

Bim and Noxa are candidates to mediate the deleterious effect of the NF-kappa B subunit RelA in cerebral ischemia.

The transcription factor nuclear factor kappaB (NF-kappaB) is well known for its antiapoptotic action. However, in some disorders, such as cerebral ischemia, a proapoptotic function of NF-kappaB has been demonstrated. To analyze which subunit of NF-kappaB is functional in cerebral ischemia, we induced focal cerebral ischemia in mice with a germline deletion of the p52 or c-Rel gene or with a conditional deletion of RelA in the brain. Only RelA deficiency reduced infarct size. Interestingly, expression of the proapoptotic BH3 (Bcl-2 homology domain 3)-only genes Bim and Noxa in cerebral ischemia depended on RelA and the upstream kinase IKK (IkappaB kinase). RelA stimulated Bim and Noxa gene transcription in primary cortical neurons and bound to the promoter of both genes. Thus, the deleterious function in cerebral ischemia is specific for the NF-kappaB subunit RelA and may be mediated through Bim and Noxa.

Animals↗
PubMed1977

Biochemical mechanism of uracil uptake regulation in Escherichia coli B. Allosteric effects on uracil phosphoribosyltransferase under stringent conditions.

The regulation of uracil uptake in bacteria was studied in bacteriophage T4-infected cells, where host-specific, stable RNA synthesis is completely shut-off by phage, and where phage-specific RNA synthesis, which is not stringently regulated, could be followed by a continuous incorporation of uracil. This incorporation into phage RNA was found to be dependent on the allelic state of the rel gene and it was thus severely restricted under stringent conditions. This was not the case with adenine, which was incorported into RNA to almost the same extent under stringent and relaxed conditions, respectively. The inhibition of uracil uptake under proceeding RNA formation, which was furthermore found to be reversed by addition of chloramphenicol, indicated a specific mechanism governing the cellular entry of uracil. This is suggested to involve the allosteric regulation of uracil phosphoribosyltransferase (EC 2.4.2.9.). The enzyme was partially purified by ammonium sulfate precipitation and gel chromatography. The dependence on GDP and GTP as positive effectors was demonstrated. The stimulatory effect of GTP was abolished in vitro by the addition of guanosine 5'-diphosphate 3-diphosphate, which is known to accumulate during amino acid starvation in stringent bacteria. The reversible inactivation of the enzyme by dilution suggested a subunit structure of uracil phosphoribosyltransferase.

Adenine↗
PubMed1976

Syntheses of elongation factors Tu and G are under stringent control in Escherichia coli.

We have compared the synthesis of the elongation factors Tu and G at 30 and 36.5 degrees in three strains of Escherichia coli: NF314 (rel+valS+), NF536 (rel+valSts), and NF537 (rel-valSts). At the elevated temperature, the latter two strains continue to grow but suffer a partial deprivation of valyl-tRNA. As a consequence, the syntheses of stable RNA, Tu, and G are decreased in NF536; the syntheses of stable RNA, Tu, and G are increased in NF537. These results indicate that the syntheses of Tu and G are directly or indirectly under the influence of the rel gene.

Escherichia coli↗