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T S Papas

Publications and source records attributed to T S Papas.

At least 109 records · Page 6Linked to original sources
PubMed1988

Lack of evidence for association of meiotic nondisjunction with particular DNA haplotypes on chromosome 21.

The hypothesis of a predisposition to meiotic nondisjunction for chromosome 21 carrying a specific molecular haplotype has been tested. The haplotype in question is defined by the restriction fragment length polymorphisms for the D21S1/D21S11 loci. Our results obtained on a sample of Northern Italian families with the occurrence of trisomy 21 (Down syndrome) failed to support this hypothesis, contradicting a previous study [Antonarakis, S. E., Kittur, S. D., Metaxotou, C., Watkins, P. C. & Patel, A. S. (1985) Proc. Natl. Acad. Sci. USA 82, 3360-3364]. These findings rule out an association between any specific D21S1/D21S11 haplotype (as well as other haplotypes for the D21S13, ETS2, and D21S23 loci) and a putative cis-acting genetic element favoring the meiotic missegregation of chromosome 21. For this reason, no preventive screening for couples at risk for trisomy 21 may be based on any of the haplotypes tested.

Adult↗
PubMed1988

Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease.

The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.

Alleles↗
PubMed1988

Mammalian ets-1 and ets-2 genes encode highly conserved proteins.

Cellular ets sequences homologous to v-ets of the avian leukemia virus E26 are highly conserved. In mammals the ets sequences are dispersed on two separate chromosomal loci, called ets-1 and ets-2. To determine the structure of these two genes and identify the open reading frames that code for the putative proteins, we have sequenced human ets-1 cDNAs and ets-2 cDNA clones obtained from both human and mouse. The human ETS1 gene is capable of encoding a protein of 441 amino acids. This protein is greater than 95% identical to the chicken c-ets-1 gene product. Thus, the human ETS1 gene is homologous to the chicken c-ets-1 gene, the protooncogene that the E26 virus transduced. Human and mouse ets-2 cDNA clones are closely related and contain open reading frames capable of encoding proteins of 469 and 468 residues, respectively. Direct comparison of these data with previously published findings indicates that ets is a family of genes whose members share distinct domains.

Amino Acid Sequence↗
PubMed1988

Expression and purification of protein segments encoded by the envelope and 3'-orf genes of human immunodeficiency virus type 1.

The pJL6 expression vector and its derivatives, pJLA16 and pANH-1, have been used for the synthesis and high-level expression in Escherichia coli of restriction enzyme fragments derived from the envelope and 3'-orf genes of the BH10 and BH8 clones, respectively, of the human immunodeficiency virus (HIV-1). These bacterially expressed proteins have been purified to apparent homogeneity by sequential detergent extraction, gel filtration, and reverse-phase high-performance liquid chromatography. The recombinant proteins have been used for the production of polyclonal and monoclonal antibodies, and the fusion proteins from the envelope gene are currently being evaluated for use as immunodiagnostic assay reagants.

Cloning, Molecular↗
PubMed1988

Comparative analysis of gp41 antigens by enzyme-linked immunosorbent assays for detecting antibodies to human immunodeficiency virus type 1.

We have compared the antigenic qualities of human immunodeficiency virus type 1 (HIV-1) gp41 glycoprotein with a synthetic oligopeptide (peptide R21S) and a bacterially synthesized protein (protein 566), which are homologous with the N-terminal region of gp41, in enzyme-linked immunosorbent assays (ELISA) for detecting antibodies to HIV-1 in sera of patients with the acquired immunodeficiency syndrome (AIDS) or the aids-related complex (ARC). Although the use of all three types of antigens readily allowed the detection of antibodies in human sera, ELISA employing purified gp41 glycoprotein and the protein 566 were more specific and sensitive than the peptide R21S ELISA.

AIDS-Related Complex↗
PubMed1988

A short-lived nuclear phosphoprotein encoded by the human ets-2 proto-oncogene is stabilized by activation of protein kinase C.

The human ets-2 gene is a homolog of the v-ets oncogene of the E26 virus and codes for a 56-kilodalton nuclear protein. The ets-2 protein is phosphorylated and has a rapid turnover, with a half-life of 20 min. When human lymphocytic CEM cells were treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the level of the ets-2 protein was quickly elevated 5- to 20-fold. This effect of TPA was mimicked by a synthetic diacylglycerol, 1-oleoyl-2-acetyl glycerol, and was blocked by the protein kinase C inhibitor H7, indicating that protein kinase C is involved in the induction. The increase in the ets-2 protein was due to stabilization of the protein, because the protein had a half-life of more than 2 h in the presence of TPA and the ets-2 mRNA level did not increase significantly upon TPA treatment. The protein synthesis inhibitor cycloheximide enhanced the effect of TPA on the ets-2 protein and could itself slow turnover of the protein. Properties of the ets-2 protein, such as nuclear localization, phosphorylation, rapid turnover, and response to protein kinase C, indicate that this protein belongs to a group of oncogene proteins which are generally thought to have regulatory functions in the nucleus (e.g., myc, fos, myb, and p53). Our results suggest that protein kinase C, either directly or indirectly, regulates the level of the ets-2 protein by posttranslational mechanisms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

c-myc can induce expression of G0/G1 transition genes.

The human c-myc oncogene was linked to the heat shock-inducible Drosophila hsp70 promoter and used to stably transfect mouse BALB/c 3T3 cells. Heat shock of the transfectants at 42 degrees C followed by recovery at 37 degrees C resulted in the appearance of the human c-myc protein which was appropriately localized to the nuclear fraction. Two-dimensional analysis of the proteins of density-arrested cells which had been heat shock treated revealed the induction of eight protein species and the repression of five protein species. All of the induced and repressed proteins were nonabundant. cDNA clones corresponding to genes induced during the G0/G1 transition were used as probes to assay for c-myc inducibility of these genes. Two anonymous sequences previously identified as serum inducible (3CH77 and 3CH92) were induced when c-myc was expressed. In response to serum stimulation, 3CH77 and 3CH92 were expressed before c-myc mRNA levels increased. However, in response to specific induction of c-myc by heat shock of serum arrested cells, 3CH77 and 3CH92 mRNA levels increased after the rise in c-myc mRNA. Therefore, we hypothesize that abnormal expression of c-myc can induce genes involved in the proliferative response.

Animals↗
PubMed1988

High expression of ets-1 gene in human thymocytes and immature T leukemic cells.

The cellular ets-1 gene homologous to the 5' region of the v-ets sequence of the E26 retrovirus codes for a 6.8-kb mRNA that is translated into a 51-kDa protein in human cells. A survey of mRNA from human tissues showed the thymus as the tissue with the highest level of ets-1 transcription, within other hematopoietic organs and tissues, including spleen, fetal liver, lymph nodes, bone marrow, and peripheral lymphocytes exhibiting low or undetectable levels of hybridization. A high level of ets-1 expression was found in murine thymocyte mRNA as well. Investigation of the ets-1 expression levels in human leukemic samples showed that primary malignant T cells (T-ALLs), corresponding to intrathymic stages of maturation, have a much higher level of ets-1 mRNA than malignant T lymphoid cells with a mature phenotype, such as adult T cell leukemias (ATLs). T-ALLs were also higher in ets-1 expression than the other lymphoid (pre-T-ALL, c-ALL, pre-B-ALL) malignant cells analyzed. Insignificant amounts of the specific ets-1 mRNA were detected in several acute myeloid leukemias representing various degrees of maturation. The elevated ets-1 mRNA in thymocytes suggests a biological role for the ets-1 product in these cells that could be explored to investigate ets-1 function. Finally, the exhibited expression of ets-1 in lymphoid cells and absence from malignant myeloid cells makes it a candidate marker for phenotyping human hematopoietic tumors.

Cell Line↗
PubMed1988

The human erg gene maps to chromosome 21, band q22: relationship to the 8; 21 translocation of acute myelogenous leukemia.

There is accumulating evidence to support that genes on chromosome 21 play an important role in the development of pathologies associated with leukemia, Down's syndrome, and Alzheimer's disease. We have previously described erg, a human gene related to the ets oncogene. In this study, we have regionally assigned the erg gene to chromosome 21q22.3 by using somatic cell hybrids and in situ hybridization analysis. In light of this chromosome assignment, the relationship of erg to the 21q translocation breakpoint characteristic of acute myelogenous leukemia (AML) was considered. By using a DNA probe that is specific for the erg gene, a panel of rodent-human cell hybrids was analyzed by the Southern technique to study specific chromosome translocations occurring in acute myeloblastic leukemia. The erg gene was found to translocate from chromosome 21 to 8 in the t(8; 21) (q22; q22), a non-random translocation found in patients with acute myelogenous leukemia of the subgroup M2 (AML-M2). The localization of the erg gene to chromosome 21q22 raises the possibility that this gene may be involved in the pathogenesis of AML-M2.

Animals↗
PubMed1988

Characterization and localization of the products of the human homologs of the v-ets oncogene.

The avian erythroblastosis virus, E26, an acute leukemia virus, contains a transforming gene composed of two cellular components, v-myb and v-ets. The v-ets related sequences of man and other mammals consist of two transcriptionally active genes, ets-1 and ets-2, located on separate chromosomes. By contrast, both of these genes are contiguous in birds, are located on the same chromosome, and are coordinately transcribed. The human ets-1 and ets-2 gene products were identified by means of antibodies directed against the ets-1 and ets-2 encoded products. A 51 kD protein has been identified as the ets-1 gene product, and a 56 kD protein as the ets-2 gene product. Cellular fractionation studies indicated that the ets-1 protein is located in the cytoplasm and the ets-2 protein is nuclear. By comparison, the chicken ets protein, which contains both the ets-1 and ets-2 domains, distributes equally between the cytoplasm and nucleus. The differential compartmentalization of the ets gene products and their non-coordinate expression suggest that these proteins have different biological functions.

Cell Compartmentation↗
PubMed1987

erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation.

The avian acute leukemia virus E26 induces a mixed erythroid-myeloid leukemia in chickens and carries two distinct oncogenes, v-myb and v-ets. Recently, a novel gene named erg, closely related to the v-ets oncogene, was identified in human COLO 320 cells and the nucleotide sequence of its approximately 5.0-kilobase transcript, erg 1 was determined. In the present study, the nucleotide sequence of the alternatively spliced transcript, erg 2, was found to differ from erg 1 by a splicing event that causes a coding frameshift near the amino terminus, resulting in an additional 99-amino acid insertion at the amino-terminus. Expression of complementary DNAs for the two transcripts in vitro resulted in synthesis of polypeptides of approximately 41 and 52 kilodaltons, suggesting the use of alternative translation initiation codons in the case of erg proteins. The erg gene was localized by somatic cell genetic analysis to human chromosome 21. It is proposed that alternative sites of splicing and polyadenylation, together with alternative sites of translation initiation, allow the synthesis of two related polypeptides from a single erg gene transcriptional unit.

Amino Acid Sequence↗
PubMed1987

The 3'-orf protein of human immunodeficiency virus shows structural homology with the phosphorylation domain of human interleukin-2 receptor and the ATP-binding site of the protein kinase family.

The primary amino acid sequence within a stretch of 25 residues (positions 91-116) of the middle portion of the 3'-orf protein (p27(3')-orf) of the human immunodeficiency virus (HIV) shares structural homology with a highly charged region within the intracytoplasmic phosphorylation domain of human interleukin-2 receptor (IL-2R) and the ATP-binding site of the catalytic subunit of cAMP-dependent protein kinase (cAMP-PK) and other members of the protein kinase family. Comparison of the predicted secondary structure within this region of p27(3')-orf with the phosphorylation domain of human IL-2R and the ATP-binding region of the phospho-kinase family of protein suggests that the 3'-orf protein could serve homologous function(s).

Adenosine Triphosphate↗
PubMed1987

Temporal and tissue-specific expression of mouse ets genes.

The expression of ets genes has been studied in mouse tissues and regenerating murine liver, an in vivo model for cell proliferation. Our results indicate that the ets-1 and ets-2 loci are transcriptionally active; the ets-2 locus encodes a major mRNA (3.5 kilobases) and is expressed in most of the tissues examined, whereas the ets-1 locus encodes a major 5.3-kilobase and minor 4.0-, 2.5-, and 2.2-kilobase RNA species and is expressed at a high level in thymus; both ets-1 and ets-2 mRNA are abundant in young proliferating tissues and are greatly reduced in terminally differentiated tissues, except thymus; compensatory growth of liver induces ets-2 mRNA before DNA synthesis, but after fos and myc induction; and ets-2 mRNA, but not ets-1 mRNA, is stabilized in the presence of cycloheximide during hepatic regeneration. These results suggest that ets-2 gene expression is intrinsically linked with cell proliferation. Thus, ets-2 expression follows a pattern similar to other members of the nuclear oncogene family. During hepatic regeneration, the ets-1 and ets-2 loci are subject to differential regulation.

Animals↗
PubMed1987

The erg gene: a human gene related to the ets oncogene.

We have isolated a cDNA clone representing the complete coding sequence of a human gene named erg, related to the ets oncogene. Nucleotide sequence analysis of this cDNA (4.6 kilobases long) revealed that this gene encodes a 363-residue protein whose predicted amino acid sequence showed a homology of approximately equal to 40% and approximately equal to 70% to two domains corresponding to the 5' and 3' regions of v-ets oncogene, respectively. A 3.2- to 3.6-kilobase and approximately equal to 5-kilobase transcript of the erg gene, which differ in size from those of the previously described Hu-ets 1 and Hu-ets 2 genes, were observed in different cells. These results suggest that the erg gene is a member of the ets oncogene family.

Amino Acid Sequence↗
PubMed1987

Expression in E. coli of erg: a novel gene in humans related to the ets oncogene.

We have recently cloned a novel human gene named erg related to the ets oncogene. In this report we describe the expression of the erg gene product in E. coli under the control of the tightly-regulated phage lambda PL promoter. Two expression vectors were utilized for the synthesis of the cII-erg and erg-fusion proteins. All these products were recognized by peptide antibodies prepared against the predicted amino acid sequences of erg and the Hu-ets-2 domain which shares homology with erg.

Amino Acid Sequence↗
PubMed1987

Molecular structure of the avian and mammalian ets genes.

The ets gene was originally identified as a second cell derived sequence transduced by the avian transforming retrovirus, E26. E26 induces erythroblastosis and myeloblastosis in chickens and transforms erythroblasts and myeloid cells in culture. From sequence analysis of the cloned provirus, the p135 transforming protein was found to be tripartite, with gag, myb and ets sequences. We have determined the nucleotide sequence of the v-ets homologous regions contained in chicken genomic clones which define nine domains. Two of these domains are not transcribed and thus do not represent functional exons. To further explore the function of the ets gene, we have begun characterization of the mammalian ets genes. Unlike the chicken gene, the mammalian ets genes are present on two chromosomes. The mammalian homologs of the 5' v-ets domain, ets-1, were mapped to chromosome 11 in man, to chromosome 9 in mouse, and to chromosome D1 in cat. The homologs of the 3' v-ets domain, ets-2, were mapped to human chromosome 21, to mouse chromosome 16, and to feline chromosome C2. The assignment of the ets-2 gene to the Down syndrome associated chromosome 21 may have interesting implications. This oncogene, ets has been connected with leukemias in chickens, and therefore might have a role in the increased frequency of leukemias in Down patients.

Amino Acid Sequence↗