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PubMed1995

Structure and transcription of the genomic locus encoding murine c-Mpl, a receptor for thrombopoietin.

We have cloned and characterised the murine gene encoding c-Mpl, a receptor for thrombopoietin and member of the hematopoietin receptor superfamily. The gene encompasses 15 kb of the mouse genome and the organisation of its 12 exons conforms closely to the pattern observed for the genes of other hematopoietin receptor family members. A site for initiation of c-mpl transcription was identified 13 nucleotides upstream of the proposed translation initiation codon. The murine mpl promoter sequence lacks conventional TATA and CAAT motifs although the transcription initiation site shares homology with the initiator sequence that specifies transcription initiation in the terminal deoxynucleotidyl transferase gene. The promoter contains consensus binding sequences for several transcriptional regulators including Ets and GATA factors, which have been implicated in control of transcription in megakaryocytes, a cell type that expresses mpl. The generation of multiple transcripts is a feature of the mpl locus. Two distinct mpl transcripts differing by an in-frame insertion of 24 nucleotides were detected in mouse spleen cells. Genomic sequence analysis identified differential splicing of alternative exon 4 sequences as the likely basis for these transcripts, which are predicted to encode receptors which differ within the first Mpl hematopoietin receptor domain.

Alternative Splicing↗

PubMed1994

Structural analysis of transcripts for the protein L-isoaspartyl methyltransferase reveals multiple transcription initiation sites and a distinct pattern of expression in mouse testis: identification of a 5'-flanking sequence with promoter activity.

The gene encoding the protein L-isoaspartyl-(D-aspartyl) methyltransferase (protein carboxyl methyltransferase, PCMT) is widely expressed in bacteria and eucaryotic cells. An antisense probe encompassing the first exon of the murine PCMT gene [E. A. Romanik, C. L. Ladino, S. C. D'Ardenne, and C. M. O'Connor (1992) Gene 118, 217-222] was used in ribonuclease protection assays to identify the initiation sites for PCMT transcription in mouse testis, brain, and liver tissues. Two major initiation sites, 155-157 nucleotides (nt) and 119 nt upstream from the ATG initiation codon, were identified in all tissues in addition to several minor sites. The locations of the initiation sites in testicular RNA were confirmed using ligation-mediated 5'-rapid amplification of cDNA ends (RACE). These initiation sites are situated at the 3'-end of a 407-bp genomic sequence which is sufficient to drive the expression of a firefly luciferase gene in transient transfection assays with NIH/3T3 cells. The 407-bp sequence resembles a housekeeping gene promoter in its high G+C content, lack of a TATA box and the presence of multiple potential binding sites for the transcription factors Sp1 and ETF. Alternative splicing in the C-terminal encoding sequence and in the 3'-untranslated regions of PCMT transcripts generates three distinct classes of mRNAs which were cloned from testicular poly(A)+ RNA using 3'-RACE. Transcript splicing either 38 nt downstream or 7 nt upstream from the termination codon in exon 7 produces mRNAs encoding PCMT isozymes with -RWK or -RDEL, respectively, at their C-termini. The predominant transcript in testis, which is not detected in somatic tissues by Northern blotting and which may be specific to germ cells, is not spliced within exon 7 and also encodes the -RWK isozyme.

3T3 Cells↗

PubMed1991

Three forms of rat basic fibroblast growth factor are made from a single mRNA and localize to the nucleus.

The molecular weight of rat basic fibroblast growth factor is predicted to be 18 kDa when the amino acid sequence is read from the single AUG initiation codon found in the cDNA. DNA sequencing upstream of this AUG codon indicated, however, that there was an extended open reading frame. In vitro translation of the rat cDNA for basic FGF gave three proteins of 18.0, 21.5, and 22.0 kDa in equal abundance. The same proteins were produced in vivo by COS cells transfected with the rat cDNA. Deletion of 81 base pairs from the reading frame upstream of the AUG codon resulted in the expression of only one protein observed at 18.0 kDa. These results indicated that the 22.0 and 21.5 kDa forms of rat basic FGF were formed when translation initiates at the alternative upstream non-AUG codons. Rat cell lines and tissues were found to express all three forms of basic FGF protein. The cDNA was used to analyze the subcellular distribution of the different forms of rat basic FGF. Subcellular fractionation and immunofluorescence of transfected COS cells showed that all three forms of the protein localized preferentially in the nucleus. Expression of a truncated cDNA from which 81 base pairs (27 amino acids) of the upstream reading frame had been deleted, showed localization of the smaller form of bFGF alone in the nucleus. These results demonstrated that although the amino acids that were deleted from the N-terminus of rat basic fibroblast growth factor have a sequence characteristic of nuclear localization motifs, they are not obligatory for the transport of the growth factor into the nucleus. Nuclear extracts taken from transfected cells also contained two smaller proteins of 16 and 12 kDa that were detected by Western blot analysis. It is possible that these are proteolytic products of bFGF.

Amino Acid Sequence↗

PubMed2000

Genomic structure and promoter analysis of the human alpha1, 6-fucosyltransferase gene (FUT8).

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1,6-fucosyltransferase (alpha1,6FucT) catalyzes the transfer of a fucosyl moiety from GDP-fucose to the asparagine-linked GlcNAc residue of complex N-glycans via alpha1,6-linkage. We have cloned the genomic DNA which encodes the human alpha1,6FucT gene ( FUT8 ) and analyzed its structure. It was found that the gene consists of at least nine exons spanning more than a 50 kbp genomic region, and the coding sequence is divided into eight exons. The translation initiation codon was located at exon 2, and thus exon 1 encodes only 5'-untranslated sequences. Transcription initiation site of FUT8 was determined by 5'-rapid amplification of the cDNA end and a primer-extension analysis using the total RNA isolated from SK-OV-3 cells, which have a high level of alpha1,6FucT activity. We then characterized the FUT8 promoter region by a reporter gene assay. The luciferase reporter assay indicated that the 5'-flanking region of exon 1, which covered about 1 kbp, conferred the promoter activity in SK-OV-3 cells. This region contains potential binding sites for some transcription factors, such as bHLH, cMyb, GATA-1, as well as a TATA-box, but not a CCAAT motif. 5'-Untranslated sequences found in ESTs and the cDNA for the FUT8 suggest the presence of an additional exon(s) at the upstream of the first exon identified in this study, and therefore, the transcription of the gene would be regulated by multiple promoters.

Base Sequence↗

PubMed1993

Fusion protein gene nucleotide sequence similarities, shared antigenic sites and phylogenetic analysis suggest that phocid distemper virus type 2 and canine distemper virus belong to the same virus entity.

Nucleotide sequencing of the fusion protein (F) gene of phocid distemper virus-2 (PDV-2), recently isolated from Baikal seals (Phoca sibirica), revealed an open reading frame (nucleotides 84 to 2075) with two potential in-frame ATG translation initiation codons. We suggest that the second in-frame ATG triplet at positions 264 to 266 initiates the translation, resulting in a protein of 537 amino acid residues with a calculated M(r) of 63,035. The putative F1/F2 cleavage site, located approximately 100 amino acid residues from the N terminus, is identical to those of the F proteins of phocid distemper virus-1 (PDV-1) isolated from European harbour seals (Phoca vitulina) and of canine distemper virus (CDV). A full scale comparison of morbillivirus F genes reveals that the conserved F0 extracellular protein-encoding region contains a large number of non-expressed mutations, suggesting that this part of the protein is under strong functional constraints. Phylogenetic analysis of morbillivirus F gene nucleotide sequences revealed a closer evolutionary relationship between PDV-2 and CDV than between PDV-1 and PDV-2. These data were supported by cross-reactivity patterns of PDV-2 and CDV obtained with monoclonal antibodies to structural proteins of PDV-1 and CDV, and suggest that PDV-2 is a strain of CDV, resulting from a trans-species infection.

Amino Acid Sequence↗

PubMed1995

Cloning and expression of a rat placental cDNA encoding a novel cathepsin L-related protein.

Cathepsin L is a major lysosomal cysteine protease produced by mouse placenta and fibroblasts. This study characterizes a novel cathepsin L-related mRNA expressed in rat placenta. Immunological and nucleotide screening of a rat placenta library identified six positive clones, the largest, pCLRP-9, being 924 base pairs in length. The combined sequences of all the clones contain an open reading frame of 711 nucleotides, a termination codon, a polyadenylation site, and 197 nucleotides of 3' untranslated region, but lack the 5' translation initiation codon. The pCLRP nucleotide sequence showed 60-64% identity to those of mouse, rat, and human cathepsin L. The deduced amino acid sequence of pCLRP codes for 237 amino acids, which align with the carboxy-terminal sequence of cathepsin L and has the active site residues characteristic of the cysteine protease family. Northern blot analysis showed hybridization of pCLRP with a major mRNA transcript of 1.3 kilobases expressed in placenta, but not kidney or liver. In contrast, a cDNA for mouse pro-cathepsin L hybridized with a transcript of 1.7 kilobases expressed in rat kidney, as well as placenta. During late gestation, steady-state levels of rat placental pCLRP mRNA were highest on day 18, whereas those of mouse procathepsin L were greatest on day 20 of gestation. Antiserum to mouse cathepsin L cross-reacted with four proteins of molecular weights 36,000 to 42,000 in rat placental culture medium, of which two were absent in the kidney. These data indicate that rat placenta expresses several species of cathepsin L-type proteins, which may be involved in placental function and nutrient supply.

Amino Acid Sequence↗

PubMed1995

Translational control of mammalian serine hydroxymethyltransferase expression.

We have investigated the role of an open reading frame upstream of and overlapping that coding for rabbit cytosolic serine hydroxymethyltransferase in the post-transcriptional regulation of enzyme expression. Elimination of the AUG codon initiating translation of the upstream open reading frame by site-directed mutagenesis (to an AUC codon) was assessed by a transfection assay in COS-1 cells. The mutation relieves translational repression with a 100-fold increase in expressed serine hydroxymethyltransferase activity compared to control-transfected cells and in the absence of any increase in the level of serine hydroxymethyltransferase mRNA. The upstream open reading frame may play a regulatory role in changing levels of expression of serine hydroxymethyltransferase through a translational control mechanism.

Amino Acid Sequence↗

PubMed1991

Characterization of genes encoding hydroxypyruvate reductase in cucumber.

Several clones corresponding to the gene encoding NADH-dependent hydroxypyruvate reductase have been isolated from a cucumber genomic library. Restriction mapping indicates the presence of two HPR genes, hpr-A and hpr-B, in the cucumber genome. Examination of the DNAs of individual plants suggests that hpr-A and hpr-B are most likely alleles at a single locus. The sequence of a 6.7 kb genomic fragment that includes the entire transcribed region, 2.2 kb of 5' flanking sequence, and about 0.8 kb of 3' flanking sequence reveals the presence of 12 introns in hpr-A. These introns are AT-rich relative to the exons. The donor sequence at the 5' end of the sixth intron contains an unusual dinucleotide, GC, rather than the nearly invariant GT. Primer extension analysis maps the transcription initiation site to 61 nucleotides upstream of the translation initiation codon. An AT-rich stretch is centered at position -31 with respect to the transcription initiation site, and a potential CCAAT box is centered at position -138. Several elements that are homologous to regulatory elements of other plant genes have been identified in the flanking regions of hpr-A.

Alcohol Oxidoreductases↗

PubMed1990

Structural organization of the human CaMIII calmodulin gene.

The complete structural organization of the human calmodulin III gene has been determined. This gene specifies the mRNA represented by the previously reported cDNA ht6. The gene contains six exons spread over a total of approx. 10 kb of DNA. Its exon-intron organization is identical to that of the only known chicken calmodulin gene and to that of two of the three characterized rat calmodulin genes. As in many other genes encoding Ca2+ binding proteins, intron 1 separates the ATG initiation codon from the remainder of the coding region. The major and two minor sites of transcription initiation have been determined by primer extension and ribonuclease protection assays. The DNA sequence in the promoter and 5' untranslated region is extremely GC-rich. No typical TATA and CAAT boxes are present upstream of the major transcriptional start site; however, a consensus CAAT box sequence is found further upstream and may play a role in transcriptional initiation from the minor start sites. Six sequence elements with high similarity to monkey SV40-like Sp1-binding regions are present in the putative promoter region, two of which contain perfect GGGCGG core sequences. The structure of the human calmodulin III gene promoter indicates that this gene belongs to a class of 'house-keeping' genes but that its level of expression may also be specifically regulated.

Amino Acid Sequence↗

PubMed1999

Structure of human ornithine decarboxylase antizyme 2 gene.

Ornithine decarboxylase antizyme 1, a negative regulator of polyamine levels, acts by destabilizing the first enzyme in the polyamine biosynthetic pathway (ODC) and by inhibiting uptake of polyamines. Recently, a second mammalian antizyme was discovered. Here, we report the genomic organization and chromosomal position of the new human gene, HuAZ2, and make a comparison with its antizyme 1 homologue. Fluorescence in-situ hybridization (FISH) localized the sequences from a bacterial artificial chromosomal (BAC) clone containing HuAZ2 at band 22 of the long arm of chromosome 15. This gene spans at least 15kb and contains five exons. No CAAT or TATA sequences could be identified within 800bp upstream of the translation initiation codon, but the 5'-flanking region contains several putative binding sites for other transcription factors. Transcription initiation of this gene appears to be heterogeneous.

5' Untranslated Regions↗

PubMed1995

Second-site suppressor mutations for the Asp-66-->Cys mutant of the transposon Tn10-encoded metal-tetracycline/H+ antiporter of Escherichia coli.

Asp66 is the only essential acidic residue in the putative hydrophilic loop2-3 region of the transposon Tn10-encoded metal-tetracycline/H+ antiporter [TetA(B)] [Yamaguchi, A., Nakatani, M., & Sawai, T. (1992a) Biochemistry 31, 8344-8348]. Escherichia coli cells producing a D66C mutant of TetA(B) showed no tetracycline resistance. A spontaneous second-site revertant was isolated from the cells carrying the D66C mutant gene, which showed moderate resistance to tetracycline [minimum inhibitory concentration (MIC), 50 micrograms/mL]. The entire sequencing of the revertant genes revealed two secondary mutations, i.e., the codon 40 of GCT (Ala)-->GAT (Asp) and T-->G at 17 bases upstream from the initiation codon of the tetA gene. There was a T-->G mutation at position -17, which was a mutation in the tet promoter/operator region, which caused a decrease in TetA(B) production. The full expression of the A40D/D66C double and the A40D single mutants, which were constructed by site-directed mutagenesis, was deleterious for cell growth. The -17T-->G mutation mitigated the deleterious effect of these mutants through reduction of expression. The -17T-->G single mutation introduced into the wild-type tet gene did not affect the level of resistance, although the expression was significantly reduced. Intact cells carrying the A40D/D66C and -17T-->G/A40D/D66C mutant plasmids showed a reduced level of tetracycline accumulation due to active efflux, whereas no significant tetracycline uptake was observed in inverted membrane vesicles prepared from these mutant-producing cells. The A40D mutation is located at opposite side of the membrane to the D66C mutation in the putative secondary structure of TetA(B). The second-site mutation might mediate its effects through a structural perturbation propagated along the polypeptide backbone.

Amino Acid Sequence↗

PubMed1989

Sequences downstream of translation start regulate quantitative expression of two petunia rbcS genes.

We investigated the basis for quantitative differences in leaf expression of the petunia genes (rbcS) encoding the small subunit of ribulose bisphosphate carboxylase. The most abundantly, SSU301, and the most weakly, SSU911, expressed petunia rbcS genes maintained their differential expression when transferred to tobacco, indicating that the determinants of quantitative expression are intrinsic to these rbcS genes. Analysis of chimeric genes in which the sequences of SSU301 and SSU911 had been exchanged at the translation start showed that sequences both 5' and 3' to the start codon contribute to differences in steady-state mRNA levels. The sequences 3' to the translation initiation codon were investigated by preparing chimeric genes in which sequences of the SSU301 and SSU911 were exchanged between each intron and at the translation termination codon. The results showed that sequences downstream of the coding region contribute to quantitative differences in expression of SSU301 and SSU911, and nuclear run-on transcription experiments indicated that the 3' sequences affect transcription rates of the rbcS genes.

Base Sequence↗

PubMedDate not supplied

Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat.

1. We have confirmed the Diabetes Mellitus OLETF type I (Dmo1) effect on hyperphagia, dyslipidaemia and obesity in the Otsuka Long-Evans Tokushima Fatty (OLETF) strain. The critical interval was narrowed down to 570 kb between D1Got258 to p162CA1 by segregation analyses using congenic lines. 2. Within the critical 570 kb region of the Dmo1 locus, we identified the G-protein-coupled receptor gene GPR10 as the causative gene mutated in the OLETF strain. The ATG translation initiation codon of GPR10 is changed into ATA in this strain and, so, is unavailable for the initiation of translation. 3. The GPR10 protein has a cognate ligand, namely prolactin-releasing peptide (PrRP). Centrally administered PrRP suppressed the food intake of congenic rats that have a Brown Norway derived Dmo1 region (i.e. with wild-type GPR10), but did not suppress that of the OLETF strain, indicating that GPR10 is without function and could explain hyperphagia in the OLETF strain. 4. Moreover, when restricted in food volume to the same level consumed by the congenic strain, OLETF rats showed few differences in the parameters of dyslipidaemia and obesity compared with congenic strains. 5. Taken together, these results demonstrate that the mutated GPR10 receptor is responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese diabetic strain rat.

Animals↗

PubMed1994

Identification of the Shine-Dalgarno sequence required for expression and translational control of the pyrC gene in Escherichia coli K-12.

Expression of the pyrC gene in Escherichia coli K-12 is regulated by a translational control mechanism in which CTP (and perhaps GTP) pool sizes determine the selection of alternative transcriptional start sites at the pyrC promoter. High CTP levels cause transcription to start primarily at a site that directs the synthesis of untranslatable pyrC transcripts. These transcripts form a hairpin at their 5' ends that blocks ribosome binding to the Shine-Dalgarno (SD) sequence. The pyrC ribosome binding site is unusual in that it contains two potential SD sequences, designated SD1 and SD2, which are located 11 and 4 nucleotides upstream of the translational initiation codon, respectively. In this study, we examined the functions of these two SD sequences in translational initiation. Mutations that inactivate either SD1 or SD2 were constructed and incorporated separately into a pyrC::lacZ protein fusion. The effects of the mutations on pyrC::lacZ expression, regulation, and transcript levels were determined. The results indicate that SD1 is the only functional pyrC SD sequence. The SD2 mutation did cause a small reduction in expression, but this effect appeared to be due to a decrease in transcript stability. In addition, we constructed a mutation that introduces a long spacer region between the hairpin at the 5' end of the pyrC transcript and a new pyrC SD sequence. As predicted by the model for translational control, this mutation caused constitutive expression of a pyrC::lacZ protein fusion.

Base Sequence↗

PubMed1987

Structure of the feline c-fes/fps proto-oncogene: genesis of a retroviral oncogene.

The nucleotide sequence of the feline c-fes/fps proto-oncogene was analyzed. Comparison with v-fes and v-fps revealed that all v-fes/fps homologous sequences were dispersed over 11 kilobase pairs in 19 interspersed segments. All segments, numbered exon 1 to exon 19 as in the chicken and human loci, were flanked by consensus splice junctions. The putative promoter region contained a CATT sequence and three CCGCCC motifs which were also found in the human locus at similar positions. About 200 nucleotides downstream of a translational stop codon in exon 19, a putative poly(A) addition signal was identified. Using the putative translation initiation codon in exon 2, a 93,000-molecular-weight protein could be deduced. This protein resembled very well the putative protein of the human c-fes/fps proto-oncogene (94% overall homology) and, although less well, the putative protein of the chicken c-fes/fps proto-oncogene (70% overall homology). As far as the feline c-fes/fps proto-oncogene sequences transduced to the Gardner-Arnstein (GA) and Snyder-Theilen (ST) strains of feline sarcoma virus (FeSV) are concerned, homology in deduced amino acid sequences between the GA- and ST-v-fes viral oncogenes and the proto-oncogene was 99%. Analysis of the recombination junctions between feline leukemia virus and v-fes sequences in GA- and ST-FeSV proviral DNA revealed for the left-hand junction the involvement of homologous recombination, presumably at the DNA level. The right-hand junction, which appeared identical in the GA-FeSV and ST-FeSV genomes, could have been the result of a site-specific recombination at the RNA level.

Animals↗

PubMed2003

Assembly of 48S translation initiation complexes from purified components with mRNAs that have some base pairing within their 5' untranslated regions.

The reconstitution of translation initiation complexes from purified components is a reliable approach to determine the complete set of essential canonical initiation factors and auxiliary proteins required for the 40S ribosomal subunit to locate the initiation codon on individual mRNAs. Until now, it has been successful mostly for formation of 48S translation initiation complexes with viral IRES elements. Among cap-dependent mRNAs, only globin mRNAs and transcripts with artificial 5' leaders were amenable to this assembly. Here, with modified conditions for the reconstitution, 48S complexes have been successfully assembled with the 5' UTR of beta-actin mRNA (84 nucleotides) and the tripartite leader of adenovirus RNAs (232 nucleotides), though the latter has been able to use only the scanning rather then the shunting model of translation initiation with canonical initiation factors. We show that initiation factor 4B is essential for mRNAs that have even a rather moderate base pairing within their 5' UTRs (with the cumulative stability of the secondary structure within the entire 5' UTR < -13 kcal/mol) and not essential for beta-globin mRNA. A recombinant eIF4B poorly substitutes for the native factor. The 5' UTRs with base-paired G residues reveal a very sharp dependence on the eIF4B concentration to form the 48S complex. The data suggest that even small variations in concentration or activity of eIF4B in mammalian cells may differentially affect the translation of different classes of cap-dependent cellular mRNAs.

5' Untranslated Regions↗

PubMed1986

Destabilization of messenger RNA/complementary DNA duplexes by the elongating 80 S ribosome.

In a previous study, we demonstrated that the ability of a cDNA fragment to hybrid-arrest the translation of its complementary mRNA in rabbit reticulocyte lysate depends on the position of the mRNA/cDNA duplex within the mRNA molecule. In the present report, we further characterize the mechanisms involved in the destabilization and subsequent translation of mRNA/cDNA hybrids by mapping in detail the positional dependence of hybrid-arrested translation of the human alpha- and beta-globin mRNAs and by directly assessing the stability of mRNA/cDNA duplexes in reticulocyte lysate under a variety of translational conditions. The mapping studies in this report demonstrate that the translation of a hybridized mRNA requires exposure of the 5' nontranslated region and the AUG initiation codon, as well as those bases 3' to the AUG which are typically protected by an initiating 80 S ribosome. The translation of these mRNA/cDNA hybrids is associated with the complete removal of cDNA from the mRNA coding region; this disruption of the mRNA/cDNA duplex is blocked by inhibitors of translational initiation and elongation. cDNAs which extend into the 3' nontranslated region remain associated with the mRNA during normal translation but are completely removed from the mRNA during translation if translational termination is suppressed. Taken together, these findings demonstrate that the disruption of mRNA/cDNA duplexes in rabbit reticulocyte lysate is tightly linked to the assembly and migration of 80 S ribosomes.

Animals↗

PubMed1998

Deregulated PAX-5 transcription from a translocated IgH promoter in marginal zone lymphoma.

The PAX-5 gene codes for the transcription factor BSAP, which is expressed throughout B-cell development. Although loss-of-function mutation in the mouse showed an essential role for Pax-5 in early B lymphopoiesis, gain-of-function mutations have implicated the human PAX-5 gene in the control of late B-cell differentiation. PAX-5 (on 9p13) has been involved together with the immunoglobulin heavy-chain (IgH) gene (on 14q32) in the recurring t(9;14)(p13;q32) translocation that is characteristic of small lymphocytic lymphoma with plasmacytoid differentiation. Here we have characterized a complex t(2;9;14)(p12;p13;q32) translocation present in a closely related non-Hodgkin's lymphoma referred to as splenic marginal zone lymphoma (MZL). In this MZL-1 translocation, the two promoters of PAX-5 were replaced on the derivative chromosome 14 by an immunoglobulin switch Smicro promoter that was linked to the structural PAX-5 gene upstream of its translation initiation codon in exon 1B. Expression analyses confirmed that PAX-5 transcription was upregulated due to efficient initiation at the Smicro promoter in the malignant B lymphocytes of patient MZL-1. For comparison we have analyzed PAX-5 expression in another B-cell lymphoma, KIS-1, indicating that transcription from the distal PAX-5 promoter was increased in this tumor in agreement with the previously characterized translocation of the immunoglobulin Emicro; enhancer adjacent to PAX-5 exon 1A. In both lymphomas, the J-chain gene, which is thought to be under negative control by BSAP, was not expressed, whereas transcription of the putative target gene p53 was unaffected by PAX-5 overexpression. Together these data indicate that the t(9;14)(p13;q32) translocation contributes to lymphoma formation as a regulatory mutation that leads to increased PAX-5 expression in late B-cell differentiation due to promoter replacement or enhancer insertion.

Aged↗