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At least 163 records · Page 9Linked to original sources

PubMed1987

Expression of hybrid (Na+ + K+)-ATPase molecules after transfection of mouse Ltk-cells with DNA encoding the beta-subunit of an avian brain sodium pump.

A cDNA encoding the beta-subunit of the (Na+ + K+)-ATPase was cloned from a chicken brain cDNA library, and its nucleotide sequence was determined. High cross-species sequence homologies were found both in coding and noncoding regions. The cDNA was subcloned into a shuttle vector derived from pSV2CAT and was stably incorporated into mouse Ltk-cells. The avian beta-subunit was expressed on the cell surface (1-8 X 10(5) molecules/cell) complexed with alpha-subunits of the murine (Na+ + K+)-ATPase. In the hybrid system there was rapid assembly of subunits, post-translational N-glycosylations of the beta-subunit at its three Asn-X-Ser (or Thr) positions, and modification of high mannose oligosaccharides to complex type. Avian beta-subunits expressed in the mouse cells had an apparent molecular weight of about 55,000 as compared with 47,000 in avian cells, due to post-translational modifications, presumably differences in complex oligosaccharides. Despite the high number of interspecies hybrid (Na+ + K+)-ATPase molecules, the cells had none of the high affinity ouabain binding sites (KD = 2 X 10(-7) M) characteristic of avian cells, consistent with the view that the ouabain binding site is located largely or exclusively on the alpha-subunit and is not greatly affected by alpha-beta interaction.

Amino Acid Sequence↗

PubMed1987

The signal sequence of an Escherichia coli outer membrane protein can mediate translocation of a not normally secreted protein across the plasma membrane.

The distal part of the long tail fibers of the Escherichia coli phage T4 consists of a dimer of protein 37. A fragment of the corresponding gene, encoding 253 amino acids, was inserted into several different sites within the cloned gene for the 325-residue outer membrane protein OmpA. In plasmid pTU T4-5 the fragment was inserted once and in pTU T4-10 tandemly twice between the codons for residues 153 and 154 of the OmpA protein. In pTU T4-22 two fragments were present, in tandem, between the codons for residues 45 and 46 of this protein. In pIN T4-6 one fragment was inserted into the ompA gene immediately following the part encoding the signal sequence. The corresponding mature proteins consist, in this order, of 605, 860, 835, and 279 amino acid residues. All precursor proteins were processed and translocated across the plasma membrane. Hence, not only can the OmpA protein serve as a vehicle for export of a nonsecretory protein, but the signal sequence alone can also mediate export of such a protein. Export of the pro-OmpA protein depends on the SecA protein. Export of the tail fiber fragment expressed from pIN T4-6 remained SecA dependent. Thus, the secA pathway in this case is chosen by the signal peptide. It is proposed that a signal peptide can mediate translocation of nonsecretory proteins as long as they are export-compatible. The inability of a signal sequence to mediate export of some proteins appears to be due to export incompatibility of the protein rather than to the absence of information, within the mature part of the polypeptide, which would be required for translocation.

Amino Acid Sequence↗

PubMed1987

Multimeric analysis of von Willebrand factor before and after desmopressin acetate (DDAVP) administration intravenously and subcutaneously in male beagle dogs.

Eight adult male Beagles were given 1 microgram of 1-deamino-8-D-arginine vasopressin (DDAVP)/kg of body weight, SC or by slow IV infusion on separate occasions. Both routes of administration induced highly significant increases (P less than 0.0001) in plasma concentrations of von Willebrand factor (vWf) antigen (Ag) and botrocetin cofactor (BCf) activity, an indication of platelet-associated vWf activity. In most instances, increases in plasma vWf:Ag and BCf values induced by SC injection were as large as or larger than those induced by slow IV infusion. With both routes of administration, BCf activity increased more than the vWf:Ag concentration, so that high BCf-to-vWf:Ag ratios were found in plasma after DDAVP administration. In plasma samples obtained before DDAVP administration, sodium dodecyl sulfate-electrophoresis resolved the vWf into a series of multimeric proteins with molecular weights similar to those of human vWf. Sodium dodecyl sulfate-electrophoresis of plasma samples obtained after DDAVP administration revealed mainly the larger molecules of vWf that were increased by DDAVP administration.

Animals↗

PubMed1987

The complete amino acid sequence of echinoidin, a lectin from the coelomic fluid of the sea urchin Anthocidaris crassispina. Homologies with mammalian and insect lectins.

The complete amino acid sequence of echinoidin, the proposed name for a lectin from the coelomic fluid of the sea urchin Anthocidaris crassispina, has been determined by sequencing the peptides obtained from tryptic, Staphylococcus aureus V8 protease, chymotryptic, and thermolysin digestions. Echinoidin is a multimeric protein (Giga, Y., Sutoh, K., and Ikai, A. (1985) Biochemistry 24, 4461-4467) whose subunit consists of a total of 147 amino acid residues and one carbohydrate chain attached to Ser38. The molecular weight of the polypeptide without carbohydrate was calculated to be 16,671. Each polypeptide chain contains seven half-cystines, and six of them form three disulfide bonds in the single polypeptide chain (Cys3-Cys14, Cys31-Cys141, and Cys116-Cys132), while Cys2 is involved in an interpolypeptide disulfide linkage. From secondary structure prediction by the method of Chou and Fasman (Chou, P. Y., and Fasman, G. D. (1974) Biochemistry 13, 211-222) the protein appears to be rich in beta-sheet and beta-turn structures and poor in alpha-helical structure. The sequence of the COOH-terminal half of echinoidin is highly homologous to those of the COOH-terminal carbohydrate recognition portions of rat liver mannose-binding protein and several other hepatic lectins. This COOH-terminal region of echinoidin is also homologous to the central portion of the lectin from the flesh fly Sarcophaga peregrina. Moreover, echinoidin contains an Arg-Gly-Asp sequence which has been proposed to be a basic functional unit in cellular recognition proteins.

Animals↗

PubMed1981

Purification and properties of a topoisomerase from Ustilago maydis.

The lower eukaryote Ustilago maydis contains a topoisomerase that removes supercoils from negative and positive superhelical DNA. The enzyme may be a multimeric protein or an aggregate of polypeptides with a native molecular weight of 270,000 as estimated by gel filtration. No cofactors are required by the enzyme, but activity is enhanced by Mg2+. Dependence of activity upon enzyme concentration is not linear. Below a threshold level where topoisomerase cannot ordinarily be detected, addition of H1 histone sharply stimulates activity. ATP and a number of structural analogues inhibit the enzyme.

Anti-Bacterial Agents↗

PubMed1995

Crystal and molecular structure at 0.16-nm resolution of the hybrid Bacillus endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase H(A16-M).

H(A16-M) is a hybrid endo-1,3-1,4-beta-D-glucan 4-glucanohydrolase from Bacillus. Its crystal structure was refined using synchrotron X-ray diffraction data up to a maximal resolution of 0.16 nm. The R value of the resulting model is 14.3% against 21,032 reflections > 2 sigma. 93% of the amino acid residues are in the most favorable regions of the Ramachandran diagram, and geometrical parameters are in accordance with other proteins solved at high resolution. As shown earlier [Keitel, T., Simon, O., Borriss, R. & Heinemann, U. (1993) Proc. Natl Acad. Sci. USA 90, 5287-5291], the protein folds into a compact jellyroll-type beta-sheet structure. A systematic analysis of the secondary structure reveals the presence of two major antiparallel beta-sheets and a three-stranded minor mixed sheet. Amino acid residues involved in catalysis and substrate binding are located inside a deep channel spanning the surface of the protein. To investigate the stereochemical cause of the observed specificity of endo-1,3-1,4-beta-D-glucan 4-glucanohydrolases towards beta-1,4 glycosyl bonds adjacent to beta-1,3 bonds, the high-resolution crystal structure has been used to model an enzyme-substrate complex. It is proposed that productive substrate binding to the subsites p1, p2 and p3 of H(A16-M) requires a beta-1,3 linkage between glucose units bound to p1 and p2.

Bacillus↗

PubMed1995

Immunoreceptor tyrosine-based activation motif is required to signal pathways of receptor-mediated growth arrest and apoptosis in murine B lymphoma cells.

The B cell Ag receptor is a multimeric protein complex consisting of the ligand binding mlg and the Ig alpha/lg beta heterodimer. The cytoplasmic tails of Ig alpha and Ig beta both contain a consensus sequence termed the immunoreceptor tyrosine-based activation motif (ITAM). This motif is believed to play a critical role in the receptor-mediated signal transduction. To explore the role of ITAM in signaling for B cell death (apoptosis), we transfected CH31 cells, an immature B lymphoma cell line, with expression vectors encoding for the CD8 extracellular/transmembrane domains and the cytoplasmic signal-transducing domain (ITAM) of Ig alpha or Ig beta, respectively. Here, we demonstrate that cross-linking of CD8:Ig alpha or CD:Ig beta with anti-CD8 mAb effectively induced cell growth arrest and apoptosis characterized by [3H]thymidine release and DNA fragmentation; in contrast, CD8:gamma 2a or truncated CD8:Ig alpha lacking the ITAM could not do so. Moreover, selective point mutation of either of the two conserved tyrosine residues within the ITAM, but not the nonconserved tyrosine, completely abrogated the ability of this motif to mediate cell death signals. These findings clearly indicate that ITAM is a critical component required for transmitting growth arrest and apoptotic signals, and that these functions of ITAM are positively regulated by tyrosine phosphorylation.

Amino Acid Sequence↗

PubMed1995

Regulation of the alpha 2(I) collagen gene transcription in fat-storing cells derived from a cirrhotic liver.

Fat-storing cells (FSC) are the main producers of type I collagen in both normal and fibrotic livers. In order to elucidate the molecular mechanisms controlling collagen expression in FSC, we examined the transcription of the alpha 2(I) collagen gene (COL1A2) in two distinct FSC clones, CFSC-2G and CFSC-5H, derived from a single CCl4-induced cirrhotic liver. The phenotype of CFSC-2G resembles freshly isolated FSC, whereas that of CFSC-5H mimics activated myofibroblasts. Cell transfection experiments showed that the upstream sequence between nucleotides -378 and -183 is essential for COL1A2 transcription in both FSC clones. This is the same promoter region that is transcriptionally active and contains the binding site of a multimeric protein complex that mediates TGF-beta stimulation of COL1A2 expression in dermal fibroblasts. We therefore examined the relative levels of endogenous and transfected COL1A2 transcription and their response to TGF-beta treatment in the two FSC clones. The results showed that CFSC-5H expresses a significantly higher level of the COL1A2 mRNA than CFSC-2G. They also showed that TGF-beta treatment increases both endogenous and transfected COL1A2 transcription in CFSC-2G but not in CFSC-5H. Interestingly, nuclear proteins from both FSC clones bind to the TGF-beta-responsive element more strongly than those from dermal fibroblasts. Altogether, the data suggest that collagen production in CFSC-5H cells has been already activated by the autocrine stimulation of TGF-beta. In contrast, CFSC-2G cells are only partially activated but can be easily recruited to produce collagen when stimulated by exogenous TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗

PubMed1995

Conserved regions in the cytoplasmic domains of the leukocyte integrin alpha L beta 2 are involved in endoplasmic reticulum retention, dimerization, and cytoskeletal association.

Selected functions of integrins, including regulated cytoskeletal association and transmembrane signaling, depend on a poorly defined bidirectional communication between the extracellular and cytoplasmic domains of the alpha and beta subunits. To investigate this problem in the leukocyte integrin alpha L beta 2 (LFA-1), we generated a series of cytoplasmic truncation or internal substitution mutants of the alpha L and beta 2 cytoplasmic domains, and assessed their biochemical and functional properties upon ectopic expression in constitutively adherent cells. Expression of the alpha L beta 2 heterodimer in stably adherent cells is sufficient to promote its constitutive cytoskeletal association. Structural determinants for such association are located in selected regions of the beta 2 cytoplasmic domain, which display functional interdependence. In addition, a conserved region (Arg733-Lys742) in the beta 2 cytoplasmic domain seems to be critical not only for its cytoskeletal association, but also for endoplasmic reticulum retention, assembly, and transport to the plasma membrane of the mature alpha L beta 2 heterodimer. Analysis of deletion mutants of the alpha L subunit demonstrates a role of the conserved, membrane-proximal GFFKR motif in conferring stability to the alpha beta complex, possibly because of its direct involvement in heterodimer formation. We propose that a previously uncharacterized association of defined subregions of the cytoplasmic domains of integrin alpha and beta subunits affects the dimerization and regulated function of the adhesion receptor.

Allosteric Regulation↗

PubMed1994

Protein kinase CK2 structure-function relationship: effects of the beta subunit on reconstitution and activity.

Protein kinase CK2 subunits alpha and beta were expressed either separately or together in a bacterial expression system (pT7-7/BL21(DE3)) and purified to homogeneity. After mixing the subunits, a CK2 holoenzyme (alpha 2 beta 2) was spontaneously reconstituted, which displays identical features as the native enzyme. The alpha subunit alone, although catalytically active by itself, has different biochemical and biophysical properties than the holoenzyme, e.g., it is extremely salt sensitive, already 50 mM monovalent salt can lead to a 50% inhibition of the catalytic activity. Furthermore, it is readily inactivated through urea, protease, and heat treatment. In contrast, the holoenzyme, either reconstituted or native, is much more stable when similar negative insults prevail. The beta subunit has at least three functions: (a) it is necessary for maximum activity of the enzyme under physiological salt conditions, (b) it protects the alpha subunit against denaturing agents or conditions, and (c) it alters the substrate specificity of the alpha subunit. By site-directed mutagenesis, certain functions of the beta subunit could be assigned to specific amino acids or domains. Twenty one mutants of the beta subunit have been prepared and assayed for their ability to assemble with the catalytic alpha subunit to give a fully competent CK2 holoenzyme. The beta subunit contains an acidic stretch (amino acid 55-64), which is obviously responsible for a negative control of enzyme activity since mutations of certain acidic amino acids within this stretch to alanine lead to a hyperactive CK2 holoenzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Modes of regulation of casein kinase II.

Casein kinase II is unique when compared to other protein kinases; it utilizes GTP with almost the same effectiveness as ATP and exists as an active holoenzyme which does not need to be activated by dissociation of regulatory subunits or unfolding of regulatory domains. In vitro, the activity of casein kinase II is inhibited by acidic compounds and stimulated by basic compounds. Casein kinase II activity is inhibited by 2,3-bisphosphoglycerate and stimulated by polyamines at levels which are physiological in red cells. To examine the effects of autophosphorylation of the beta subunit on activity, two mutants of the Drosophila beta subunit have been constructed in which Ser-4 or Ser-(2-4) are changed to alanine residues. Analysis of autophosphorylation with wild-type and mutant recombinant holoenzymes reveals Ser-2 and Ser-3 as the major autophosphorylation sites. Autophosphorylation does not affect the phosphorylation of casein, but reduces the rate of phosphorylation of glycogen synthase by 30%, elongation factor I by 50-70%, and calmodulin by 20-40%. The data indicate that autophosphorylation of the beta subunit can negatively regulate the phosphotransferase activity of casein kinase II with physiological substrates. To examine regulation of casein kinase II activity by the beta subunit, recombinant alpha and beta subunits from human and Drosophila were expressed in Escherichia coli. Upon formation of the holoenzyme, the beta subunit stimulated the catalytic activity 4- to 5-fold. The catalytic alpha subunit contains the eleven conserved subdomains characteristic of all protein kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗

PubMed1994

Aggregation of the intracellular domain of the type 1 tumor necrosis factor receptor defined by the two-hybrid system.

The yeast-based two hybrid system has been used to determine whether oligomerization of the intracellular domain of the 55-kDa type 1 tumor necrosis factor (TNF) receptor may occur during TNF action. This assay depends upon reconstitution of the function of the GAL4 transcriptional activator through interaction of a protein fused to the GAL4 DNA binding domain with a protein fused to the transcriptional activation domain of GAL4. Fusion of the type 1 TNF receptor intracellular domain with the DNA binding domain and the transactivation domain of GAL4 led to activation of the lacZ indicator gene, demonstrating interaction of the receptor intracellular domain with itself. A HeLa cell cDNA library was searched for proteins that interact with the intracellular domain of the type 1 TNF receptor. A protein corresponding to amino acids 329-426 in the type 1 TNF receptor intracellular domain was identified by this screen. The aggregation domain was further defined by testing the ability of deletion mutants of the type 1 TNF receptor intracellular region to interact with the complete intracellular domain. These experiments map the aggregation domain to a sequence of amino acids previously shown to be responsible for mediating TNF-induced cytotoxicity. These results suggest that aggregation of type 1 TNF receptor intracellular domains may be important in TNF signal transduction.

Cloning, Molecular↗

PubMed1988

Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin).

A binding protein for plasminogen activator inhibitor 1 (PAI-1-BP) was isolated from human plasma by a four-step procedure. 1) The 7 S globulin fraction of plasma was isolated by gel filtration on Sephacryl S-300. 2) Human endothelial cell-type plasminogen activator inhibitor (PAI-1), pretreated with 12 M urea, was added to this fraction (22 micrograms of PAI-1/ml of plasma), and a PAI-1 antigen peak with apparent mass 450 kDa (representing 65% of PAI-1 antigen and 85% of PAI activity) was isolated by gel filtration of this mixture. 3) The PAI-1.PAI-1-BP complex was further purified by immunoadsorption on an immobilized murine monoclonal antibody directed against PAI-1 (MA-7D4) and by elution with 4 M KSCN. 4) The complex was then dissociated by addition of excess human tissue-type plasminogen activator (t-PA), and t-PA and PAI-1 antigen (t-PA.PAI-1 complexes and free t-PA and PAI-1) were removed by immunoadsorption on monoclonal antibodies directed against t-PA (MA-62E8) and against PAI-1 (MA-7D4 and MA-12A4). Sodium dodecyl sulfate-gel electrophoresis of the purified material under nonreducing conditions revealed two bands with apparent mass approximately equal to 150 kDa and two bands with mass 74 and 68 kDa. Reduced sodium dodecyl sulfate-gel electrophoresis displayed two main bands with apparent masses of 73 and 64 kDa. The PAI-1-BP reacts with urea-treated, but not with inactive PAI-1. t-PA dissociates the complex between PAI-1 and PAI-1-BP. PAI-1 in complex with PAI-1-BP is 2-3-fold more stable at 37 degrees C than purified PAI-1, suggesting that PAI-1-BP may stabilize PAI-1 in blood. The concentration of PAI-1-BP in plasma determined by titration with PAI-1 is approximately 130 mg/liter. The isolated PAI-1-BP was shown to be identical to S protein (vitronectin) both by cross-reactivity with monospecific rabbit antisera and by NH2-terminal amino acid sequence analysis. The gel filtration behavior, mobility on sodium dodecyl sulfate-gel electrophoresis, and concentration in plasma suggest that PAI-1-BP is a multimer (presumably a dimer) of S protein accounting for approximately 35% of the S protein in plasma.

Amino Acids↗

PubMed1984

Negative complementation of recA protein by recA1 polypeptide: in vivo recombination requires a multimeric form of recA protein.

Recombination in vivo was studied in recA- heterozygous lacZ merodiploids by performing beta-galactosidase assays after infection with lambda precA+. Recombination as measured by beta-galactosidase production was a linear function of lambda pecA+ multiplicity of infection (MOI) when the strain contained a deletion of the chromosomal recA gene. However, when the strain carried a recA1 missense allele, a higher lambda precA+ MOI was required to obtain levels of recombination comparable to the delta (recA) strain, and the slope of the dose-response curve increased to approximately two. It is proposed that negative complementation occurs in mixed tetramers of wild-type and missense recA polypeptides, and that in vivo recombination is a property of a multimeric form of recA protein.

Alleles↗

PubMed1993

A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2: divergence of CD2 ligands during the evolution of humans and mice.

To search for possible ligands of CD2 distinct from CD58 (lymphocyte function-associated antigen 3), we have produced a soluble pentameric CD2-immunoglobulin (Ig) fusion protein (spCD2) linking the 182-amino acid human CD2 extracellular segment with CH2-CH3-CH4 domains of human IgM heavy chain, thus enhancing the micromolar affinity of the CD2 monomer through multimeric interaction. Using quantitative immunofluorescence and standard stringency wash conditions, we observed that the binding of spCD2 to human B lymphoblastoid JY cells and red blood cells is virtually inhibited by anti-CD58 TS2/9 monoclonal antibody, even though these cells express levels of CD48 and CD59 comparable to CD58. Consistent with these results, spCD2 did not show any binding to Chinese hamster ovary (CHO) cells transfected with human CD48 or CD59. However, binding studies on CD48-, CD58-, or CD59-transfected CHO cells with spCD2 under low stringency wash conditions revealed that human CD48 is a low affinity ligand of human CD2 compared with CD58 (Kd approximately 10(-4) vs. approximately 10(-6) M, respectively). The findings are noteworthy given that in the murine system CD48 is the major ligand for CD2. No detectable binding was observed to CD59-transfected CHO cells despite a report suggesting that CD59 may bind to the human CD2 adhesion domain. Importantly, in cell-cell adhesion assays between CD2+ Jurkat T cells and CD48- or CD59-transfected CHO cells, there was no conjugate formation, whereas binding of Jurkat T cells to CD58-transfected CHO cells was readily detected. Collectively, our findings provide evidence for a conservation of the CD2-CD48 interaction in the human species that may be of limited, if any, functional significance. Given the importance of the CD2-CD48 interaction in the murine system and CD2-CD58 interaction in humans, it would appear that there has been a divergence of functional CD2 ligands during the evolution of humans and mice.

Animals↗

PubMed1995

The multimeric nonstructural NS2 proteins of bluetongue virus, African horsesickness virus, and epizootic hemorrhagic disease virus differ in their single-stranded RNA-binding ability.

The structure and single-stranded (ss) RNA-binding by the nonstructural protein NS2 of three different orbiviruses were studied and compared. African horsesickness virus (AHSV), bluetongue virus (BTV), and epizootic hemorrhagic disease virus (EHDV) were analyzed in recombinant baculovirus-infected cells and in cells infected with BTV and AHSV. Sedimentation analysis and nonreducing SDS-PAGE revealed that NS2 of all three orbiviruses is a 7S multimer with both inter- and intramolecular disulfide bonds, probably consisting of six or more NS2 molecules. The 7S NS2 multimer of all three viruses binds ssRNA but there is a marked disparity in the ssRNA-binding ability between the three proteins. At physiological salt concentration, BTV NS2 binds ssRNA very efficiently, whereas AHSV NS2 shows only a low efficiency for binding ssRNA. EHDV NS2 binds with intermediate efficiency. The result was the same irrespective of whether poly(U)-Sepharose or viral mRNA was used, indicating that ssRNA-binding by NS2 is nonspecific. The difference in RNA-binding ability may be related to the alpha-helix content of the respective proteins. NS2 of BTV has the highest predicted alpha-helix content followed by EHDV and AHSV. The ability of the NS2 proteins to form virus inclusion body-like structures in baculovirus-infected cells is not affected by the ssRNA-binding disparity.

African Horse Sickness Virus↗

PubMed1983

Two unrelated cell-derived sequences in the genome of avian leukemia and carcinoma inducing retrovirus MH2.

Molecularly cloned proviral DNA of avian replication-defective retrovirus Mill Hill No. 2 (MH2) was analyzed. The MH2 provirus measures 5.5 kb including two long terminal repeats (LTR), and contains a partial complement of the structural gene gag, 1.5 kb in size, near the 5' terminus, and a 1.3-kb segment of the v-myc transforming gene near the 3' terminus. These v-myc sequences are closely related to the v-myc transforming gene of avian acute leukemia virus MC29, and to the cellular chicken gene c-myc. The gag and myc domains on the MH2 provirus are separated by unique sequences, 1.3 kb in size and termed v-mil, which are unrelated to v-myc, or to other oncogenes or structural genes of the avian leukemia-sarcoma group of retroviruses. Normal chicken DNA contains sequences closely related to v-mil, termed c-mil. Analyses of chicken c-mil clones isolated from a recombinant DNA library of the chicken genome reveal that c-mil is a single genetic locus with a complex split gene structure. In the MH2 genome, v-mil is expressed via genome-sized mRNA as a gag-related hybrid protein, p100gag-mil, while v-myc is apparently expressed via subgenomic mRNA independently from major coding regions of structural genes. The presence in the MH2 genome of two unrelated cell-derived sequences and their independent expression may be significant for the oncogenic specificities of this virus.

Animals↗

PubMed1994

Assignment of the human MAD and MXI1 genes to chromosomes 2p12-p13 and 10q24-q25.

MAD and MXI1, two recently described members of the basic helix-loop-helix (bHLH) gene family, encode proteins that dimerize with and modulate the DNA binding of max. In turn, mad-max or mxi1-max heterodimers or max homodimers can compete for DNA binding sites with dimers formed between max and myc oncoproteins and antagonize the transcriptional activities of this latter class of proteins. Using a combination of somatic cell mapping and fluorescence in situ hybridization techniques, we have determined the chromosomal locations of the MAD and MXI1 genes. The MAD gene maps to chromosome 2p12-p13, a region involved in translocations and deletions in acute and chronic lymphocytic leukemias as well as non-lymphocytic leukemias and Hodgkin disease. The MXI1 gene localizes to chromosome 10q24-q25, a region involved in translocations and deletions in acute and chronic lymphocytic leukemias and prostatic carcinomas. The availability of genomic clones of MAD and MXI1 will permit an assessment of their involvement in these diseases at the molecular level.

Animals↗