PubMed Health⌕ Search

Biomedical subjects

A Begue

Publications and source records attributed to A Begue.

30 records · Page 2Linked to original sources
PubMed1992

Phylogeny of the p68c-ets-1 amino-terminal transactivating domain reveals some highly conserved structural features.

The chicken c-ets-1 locus gives rise to two distinct transcription factors differing only in their structurally and functionally unrelated N-termini. One of these transcription factors, p54c-ets-1, contains a specific, short (27 amino acids), hydrophilic N-terminus encoded by a single exon, I54, that is widely conserved among vertebrates. The other one, p68c-ets-1, the cellular counterpart of the viral ets oncogene product, differs in the replacement of the I54 by two exons, termed alpha and beta, encoding a larger (71 amino acids), hydrophobic N-terminus which, in contrast to I54, exhibits properties of a transactivating domain. To date the alpha and beta exons have only been found in chicken. Here, we demonstrate the existence of the alpha and beta exons in other avian species (quail and duck) and the existence of the alpha exon in reptiles (turtle). However, none of them could be detected in mammals. Our results strongly suggest that, in contrast to the phylogenetically well-conserved I54 exon, the alpha exon is restricted to reptilian species (birds and 'true' reptiles), whereas the beta exon is detectable so far only in birds. Comparison of their amino acid sequences reveals that the alpha exon and to a much greater extent the beta exon have diverged faster than the I54 exon. In addition, we show that the N- and C-terminal thirds of the alpha exon and the highly hydrophobic nature of the alpha beta-encoded sequence are heavily conserved features and thus likely to be required for function as a transactivating domain in p68c-ets-1 and possibly in the viral P135gag-myb-ets transforming protein.

Amino Acid Sequence↗
PubMed1991

Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene.

The thyroid hormone receptor alpha (THRA or c-erbA-1) gene belongs to a family of genes which encode nuclear receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. These receptors are composed of several domains important for hormone-binding, DNA-binding, dimerization and activation of transcription. We show here that the human THRA gene is organized in 10 exons distributed along 27 kbp of genomic DNA on chromosome 17. The position of the introns in human THRA is highly conserved when compared to the chicken gene despite their differing lengths. The N-terminal A/B domain as well as the 5' untranslated region is encoded by two exons. Interestingly, each of the putative zinc fingers of the receptor DNA-binding domain is encoded by one exon and the hormone-binding domain is assembled from three exons. The two last exons of the gene are alternatively spliced to generate two different messenger RNAs. In addition, we confirm that another gene, belonging to the nuclear receptor superfamily, ear-1, overlaps with the 3' region of THRA in an opposite transcriptional orientation.

Amino Acid Sequence↗
PubMed1990

The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation.

Cell transformation by oncogenes leads to changes in gene expression. A key event in this process seems to be activation of the transcription factors AP-1 and PEA 3. Their synergistic activities are required for efficient activation of transcription from different promoters by many different oncogenes, serum growth factors and the tumour promoter TPA. We show here that the products of the ets-1 and -2 proto-oncogenes, whose biological function was previously unknown, are transcription factors that activate transcription through the PEA 3 motif. The p68c-ets-1 protein specifically binds to DNA and contains a transcriptional activation domain. The ets-like gene family therefore seems to encode a new family of transcription factors, apparently unrelated to other transcription factors. The p68c-ets-1 protein cooperates with c-Fos and c-Jun (components of AP-1) for activation of transcription from the oncogene-responsive domain of the polyoma enhancer, indicating that combined activity of all three oncoproteins could be involved in the response of cells to growth stimuli.

Base Sequence↗
PubMed1989

Definition of an Ets1 protein domain required for nuclear localization in cells and DNA-binding activity in vitro.

Ets1 and Ets2 are nuclear phosphoproteins which bind to DNA in vitro and share two domains of strong identity. Deletion analyses of each of these conserved regions in Ets1 demonstrated that integrity of the carboxy-terminal domain, also conserved in the more distantly related elk and erg gene products, is essential for both nuclear targeting and DNA-binding activity in vitro.

Animals↗
PubMed1988

Identification in chickens of an evolutionarily conserved cellular ets-2 gene (c-ets-2) encoding nuclear proteins related to the products of the c-ets proto-oncogene.

In chicken cells, we previously identified a set of proteins (p58-64) structurally related to, but distinct from, the products encoded by the c-ets proto-oncogene. We report here the isolation and nucleotide sequence of a cDNA encoding nuclear products of mol. wt 58, 60, 62 and 64 kd, indistinguishable from those detected in chicken cells. The p60 and p64 species appear to represent phosphorylated versions on serine and threonine residues of p58 and p62. The homology of p58-64 to other ets-related proteins, including the v-ets encoded domain of the transforming protein of avian leukemia virus E26 and p54c-ets, the translation product of the chicken (Ck) c-ets gene, is confined to two regions of 175 and 96 amino acid residues localized respectively at the carboxy-terminal domain and close to the amino-terminal domain of these molecules. This cDNA corresponds to a gene localized in a locus distinct from that of c-ets which is transcribed as a 4.0-kb RNA species in most chicken tissues. We also identified the human (Hu) c-ets-2-encoded products as two proteins of 60 and 62 kd, highly related to chicken p58-64. This, together with the fact that the amino acid sequence of the cDNA encoding p58-64 is 95% identical to the reported partial sequence of a Hu-c-ets-2 cDNA, indicates that p58-64 are the translation products of the Ck-c-ets-2 gene.

Amino Acid Sequence↗
PubMed1988

Alternative splicing of RNAs transcribed from the chicken c-mil gene.

Two distinct c-mil-related cDNA clones have been isolated from a chicken embryo cDNA library. Results presented here show that the single chicken c-mil gene is coding for two c-mil mRNA species, different by at least 60 base pairs and generated by an alternative splicing mechanism. These mRNA molecules can be translated into two distinct proteins of 73 and 71 kilodaltons.

Amino Acid Sequence↗
PubMed1986

Characterization of a myc-containing retrovirus generated by propagation of an MH2 viral subgenomic RNA.

We have previously isolated, from wild-type MH2 virus that contains the two oncogenes mil and myc, mutants defective in one or the other oncogene product. We report here the molecular cloning and extensive characterization of MH2 CL25 provirus lacking the v-mil oncogene. Our results indicate that this virus corresponds to the propagation of the 2.8-kilobase subgenomic RNA of MH21.

Base Sequence↗
PubMed1986

[Preparation and characterization of specific antisera directed against different polypeptide domains encoded by the c-myc oncogene for studying the expression of this gene introduced into quail or rat cells].

By using bacterial expression vectors, we have prepared antisera directed against two polypeptidic domains encoded by exons 2 and 3 of the human c-myc oncogene. These antisera which detect specifically the human c-myc proteins allow us to analyse the expression of human c-myc gene activated by retroviral sequences and introduced in quail embryo cells (QEC) or in established rat embryo fibroblastic cell line (208 F). Although human myc mRNA are expressed in the two cell types, the p64/p67 human c-myc proteins are only detected in the QEC.

Animals↗
PubMed1984

Increased transcription of the c-myc oncogene in two methylcholanthrene-induced quail fibroblastic cell lines.

The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activation observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analysed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as compared with that of the other cell lines tested that show low levels of c-myc transcripts. Our results suggest that one of the ways methylcholantrene could mediate transformation is by inducing an abnormal regulation of the c-myc gene.

Animals↗
PubMed1983

The human DNA locus related to the oncogene myb of avian myeloblastosis virus (AMV): molecular cloning and structural characterization.

Chicken and human cell DNA contains sequences homologous to the avian myeloblastosis virus oncogene, v-myb. These cellular sequences, c-myb (human) and c-myb (chicken), were isolated from libraries of human or chicken cell DNA fragments, generated by partial digestion with the restriction enzymes AluI and HaeIII, and compared. The chicken c-myb locus isolated from two distinct overlapping recombinant phages, contained five contiguous EcoRI fragments of 5.4, 1.1, 2.1, 2.2 and 9 kbp, accounting for all the bands seen with a v-myb probe in a complete EcoRI digest of chicken cellular DNA. Likewise, the screening of the human library yielded a recombinant phage hybridizing with the v-myb specific probe, that contained five EcoRI fragments of 2.8, 2.6, 2.0, 1.2 and 5.0 kbp (the last ending with an artificial EcoRI site, due to the construction of the library) belonging to the c-myb (human) locus. Probes using the EcoRI chicken DNA cloned fragments revealed corresponding contiguous EcoRI fragments in the human clone. Subsequent analyses of cellular polyadenylated mRNA extracted from human and chicken cells allowed the identification of single RNA species of 3.8 and 4.0 kb, respectively, as the representative transcripts of the c-myb locus in the two species. Thus, c-myb appears as a single locus in man and chicken, conserved with a similar structure in the two distantly related species. Our preparation of a specific human c-myb probe with an increased sensitivity on DNA/RNA blots should facilitate analyses concerning this gene in human normal or tumour cells or tissues.

Animals↗
PubMed1982

Molecular cloning and characterization of the chicken DNA locus related to the oncogene erbB of avian erythroblastosis virus.

Chicken cell DNA contains sequences which are homologous to the avian erythroblastosis virus oncogene v-erb. These cellular sequences (c-erb) have been isolated from a library of chicken cell DNA fragments generated by partial digestion with AluI and HaeIII and shown to be shared by at least two loci in the chicken DNA. One of them, denoted c-erbB, contains approximately 1.8 kilobase pairs of chicken DNA homologous to the 3' part of the v-erb oncogene (v-erbB). Restriction mapping studies show that the c-erbB DNA sequences homologous to v-erbB are distributed among six EcoRI fragments located in a single genomic region. Heteroduplexes between v-erbB in viral RNA and cloned c-erbB DNA show that the chicken DNA sequences homologous to v-erbB are interrupted by 11 DNA sequences not present in the v-erb oncogene. We conclude from our data that the c-erbB locus might represent the cellular progenitor for the v-erbB domain of the v-erb oncogene.

Alpharetrovirus↗