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A Tavitian

Publications and source records attributed to A Tavitian.

At least 73 records · Page 4Linked to original sources

Chromosome mapping of the human ras-related rab3A gene to 19p13.2.

The rab genes belong to one of the three main branches of the ras super family. The encoded rab proteins share 38 to 75% amino acid identity with the yeast YPT1 and SEC4 proteins. We used the human rab3A cDNA to map the corresponding gene on human chromosomes by chromosome sorting and in situ hybridization. Both techniques allowed the assignment of the rab3A gene to chromosome 19 with a regional localization on 19p13.2 obtained by in situ hybridization.

Chromosome Banding↗

The putative oncogene Spi-1: murine chromosomal localization and transcriptional activation in murine acute erythroleukemias.

We have shown previously that spleen focus forming virus integration near the Spi-1 putative oncogene is observed in 95% of erythroid Friend tumors (Moreau-Gachelin et al., 1988). Here we describe how the proviral insertion in the Spi-1 domain is associated with the enhanced transcription of a 1.4 kb mRNA normally expressed at a low level in normal cells. The gene is localized on murine chromosome 2, band E3. The structure of the Spi-1 gene was determined by sequencing genomic and cDNA clones. The gene has an open reading frame encoding a protein of 218 amino acids, extending over five exons. Proviruses always integrate outside, upstream and in the opposite orientation of the protein-encoding domain. This suggests that SFFV integration activates the expression of Spi-2 gene that may contribute to the erythroleukemic process.

Amino Acid Sequence↗

Spi-1 is a putative oncogene in virally induced murine erythroleukaemias.

Retroviral insertional mutagenesis has been proposed as an efficient mechanism to turn on or to increase the expression of oncogenes in several avian or mammal models. Integration site studies of avian leukosis virus, murine leukaemia and murine mammary tumour viruses led to the coleutification of highly conserved genes whose expression is induced or increased during leukaemogenesis, probably through enhancer elements present in the retroviral long terminal repeats. This is reminiscent of the activation of cellular proto-oncogenes or putative oncogenes in numerous human tumours and leukaemias as a result of chromosomal translocations or DNA rearrangements. Here we report the characterization of a new putative oncogene isolated from a murine erythroleukaemia induced by the acute leukaemogenic retrovirus spleen focus forming virus (SFFV). An important and unusual feature of this genomic locus Spi-1 (for SFFV proviral integration) is that rearrangements due to SFFV integration were found in 95% of the erythroid tumours studied. A 4.0-kilobase messenger RNA was detected in rearranged tumours. No Spi-1 rearrangement was detected in other virally induced myeloid, lymphoid or erythroid tumours tested.

Animals↗

The ras-related ral gene maps to chromosome 7p15-22.

Human cDNAs coding for the new protein ral that shares 50% homology with the ras proteins have been recently isolated. A 600-bp fragment carrying mainly the coding region was used to localize the ral gene by hybridization with sorted chromosomes and in situ hybridization. Direct molecular hybridization on sorted chromosomes using a single laser illumination allowed the assignment of the ral gene to a region of the flow karyotype containing chromosomes 7, 8 and X. With dual laser analysis ral was assigned to the fraction containing chromosome 7. In the 331 human metaphases hybridized with the 3H-labelled insert, the silver grain distribution showed a unique major signal on chromosome 7p15-22.

Cell Line, Transformed↗

Expression of the ras-related ralA, rho12 and rab genes in adult mouse tissues.

The expression of recently isolated mammalian ras-related ral, rho, and rab genes was examined in adult mouse tissues. Most of the genes studied were transcribed into two major messenger RNAs. The transcription of each gene appeared to be regulated in a complex manner with a tissue-specific modulation of the two transcripts. One member of the rab gene family, rab3, showed an RNA expression restricted to brain-tissues. Ral, rho, and three other rab genes had a more ubiquitous expression in murine tissues. However, the expression level of each gene showed a high degree of variation depending upon the organ. Among all the members of the enlarged ras gene family examined so far, the rab3 gene is the first example showing an expression restricted to a distinct organ.

DNA↗

Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region.

We have characterized two new ras-related genes rap1 and rap2 from a human cDNA library, by hybridization with the Drosophila Dras3 gene at low stringency conditions. The rap1 and rap2 genes encode proteins of 184 and 183 amino acid respectively with molecular weights of 20.9 kd and 20.7 kd. These proteins are 53% and 46% identical to the human K-ras protein and share several properties with the classical ras proteins. The C-terminal cysteine involved in the membrane anchoring as well as the GTP binding regions of the p21 ras proteins are present in the rap proteins suggesting that these proteins could bind GTP/GDP and have a membrane localization. The most striking difference between the rap and ras proteins resides in their 61st amino acid. As in the Drosophila Dras3 protein, both rap proteins have a threonine instead of the glutamine found at position 61 of the classical ras proteins. Furthermore the putative effector domain of the ras proteins is strictly conserved in the rap1 protein whereas only one amino acid difference is found in the rap2 protein. This suggests that the rap proteins might interact with the same effector as the ras proteins.

Amino Acid Sequence↗

Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library.

Several oligonucleotide mixtures corresponding to a 6-amino acid sequence that is strictly conserved in all the ras and ras-related proteins (from various organisms) were tested for their ability to hybridize to 11 cloned members of the ras gene superfamily. Among these mixtures, a combination of two sets of partially complementary oligomers were able to hybridize to all the tested sequences. To identify members of the ras superfamily, we screened a rat brain cDNA library with these probes and isolated four genes, denoted rab1, -2, -3, and -4, encoding proteins homologous to the yeast YPT protein. Amino acid homology scores with YPT range from 75% for rab1 to 37% for rab4, whereas the homologies with p21 ras and other ras-related proteins are approximately equal to 30%, and homologous residues were clustered in the regions involved in GTP/GDP binding. Another striking similarity shared by the rab and the other ras-related proteins is the conservation of at least one cysteine residue near the carboxyl-terminal end involved in the membrane binding of the ras proteins. rab1 is a mammalian homolog of the yeast YPT gene, and the four rab genes constitute an additional branch of the ras gene superfamily that to our knowledge has not been described in higher eukaryotes.

Amino Acid Sequence↗

Presence of a c-myc transcript initiated in intron 1 in Friend erythroleukemia cells and in other murine cell types with no evidence of c-myc gene rearrangement.

In Friend murine erythroleukemia cells, although no detectable c-myc gene rearrangement was found, we observed, in addition to the normal 2.3-kilobase c-myc transcript, the presence of a 2.3-kilobase c-myc mRNA initiated in intron 1 at a promoter site called P3. The intron 1-initiated transcript has a longer half-life than the normal c-myc mRNA. This c-myc transcript initiated in intron 1 was also found in other murine cell types where no rearrangement of the c-myc locus has been reported.

Animals↗

Structure and expression of the chicken epidermal growth factor receptor gene locus.

Similarity between the carboxyl-terminal portion of the human epidermal growth factor (EGF) receptor and the deduced protein sequence of the chicken-derived oncogene v-erbB, of avian erythroblastosis virus strain H, has suggested that the chicken cellular erbB locus, c-erbB, might be part of a longer EGF-receptor gene in the chicken, whose entire coding capacity remained to be defined. The c-erbB locus spans more than 20 X 10(3) base pairs (20 kbp) of DNA and contains at least 1.8 kbp homologous to the v-erbB oncogene. We show here that human EGF receptor cDNA and chicken genomic DNA share homology not only within the c-erbB locus but also within a 25.1-kbp DNA region situated 5' to this locus. The 3' region of the EGF receptor overlaps, in sequence homology, the c-erbB locus. The EGF receptor/c-erbB locus in chicken generates six related but distinctly different mRNAs of sizes 12, 9, 5, 3.6, 3.2 and 2.6 kb. The transcripts of 12, 9, and 3.6 kb contain sequences coding for both the extracellular EGF-binding domain of the receptor and the intracellular tyrosine kinase domain. The 12-kb and 9-kb transcripts, which have already been shown to contain the sequences coding for the v-erbB, were found to possess, in addition, sequences that encode the entire chicken EGF receptor. The 3.2-kb and 2.6-kb mRNAs are homologous only to the 5' portion of the EGF receptor gene. These results therefore indicate that the c-erbB locus, initially defined by homology to the viral transforming gene, corresponds to the 3' region of the EGF receptor gene in the chicken genome. The multiple, related, chicken EGF receptor RNA transcripts reported here are reminiscent of the various human EGF receptor RNA transcripts observed in normal and transformed cells.

Alpharetrovirus↗

The ral gene: a new ras related gene isolated by the use of a synthetic probe.

We synthesized a set of 20-mer oligonucleotides corresponding to a sequence of seven amino acids strictly conserved in all the different ras proteins, from yeast to man, as well as in rho and YPT, two proteins distantly related to p21 ras (approximately 30% amino acid homology). This oligonucleotide probe was used to search for new members of the ras family. We describe here a new ras related gene named ral, isolated from a cDNA library of immortalized simian B-lymphocytes. The ral gene codes for a 206 amino acid protein of expected mol. wt 23.5 kd that shares greater than 50% homology with H-ras, K-ras or N-ras. The GTP binding regions of p21 ras and a C-terminal cysteine involved in membrane anchoring are also present in ral; this strongly suggests that ral is a GTP binding protein with membrane localization. Furthermore, several external regions of p21 ras presumably involved in the interaction with effector, receptor and/or regulatory proteins are highly homologous to the corresponding regions in ral. Therefore some of the proteins that interact with ral might be identical or closely related to those interacting with p21 ras.

Amino Acid Sequence↗

Focal esophageal candidiasis in acquired immunodeficiency syndrome (AIDS).

When candidiasis involves the esophagus, it usually does so as an extensive and diffuse infection. In our experience, however, esophageal candidiasis in patients with the acquired immunodeficiency syndrome (AIDS) is clinically distinct from the same infection in patients with other immunodeficiency states. Of 25 patients with AIDS and esophageal candidiasis studied radiographically, 4 patients with localized involvement of the esophagus are presented. The clinical and radiologic manifestations of focal esophageal candidiasis in these patients are reviewed and compared to previously described cases of esophageal candidiasis.

Acquired Immunodeficiency Syndrome↗

Ketoconazole-resistant Candida esophagitis in patients with acquired immunodeficiency syndrome.

Although ketoconazole has been shown to be effective in treating esophageal candidiasis in other immunodeficiency states, similar studies have not been reported in patients with acquired immunodeficiency syndrome. Six patients with acquired immunodeficiency syndrome and oral and esophageal candidiasis who had been treated with ketoconazole for more than 2 mo were evaluated with barium esophagram and endoscopy with biopsy and brush cytology. All of the patients had persistent Candida esophagitis. In 2 patients, fungal cultures and sensitivity testing indicated Candida albicans resistant to ketoconazole in vitro. In patients with acquired immunodeficiency syndrome, esophageal candidiasis may not resolve with up to 6 mo of ketoconazole therapy and may require more vigorous antifungal therapy than in patients with other immunodeficiency states.

Acquired Immunodeficiency Syndrome↗

Isolation from the spleen of myeloproliferative sarcoma virus-infected mice of a myelomonocytic tumor cell line secreting hematopoietic colony stimulating factors.

Clonogenic tumor cells were detected in the spleen of DBA/2 mice infected with the myeloproliferative sarcoma virus (MPSV). These cells could be isolated because of their ability to proliferate on the greater omentum of sublethally irradiated isogenic recipient mice. We have established a permanent suspension myelomonocytic cell line in vitro (TE8), from a tumor obtained after subcutaneous transplantation of the omental tumor masses. The TE8 cells are clonogenic in semi-solid medium containing agarose. The colonies thus obtained gave rise to myelomonocytic cell lines growing in suspension in liquid medium. One of those cloned cell lines, C1(1011) was studied in details. It is exclusively composed of initial donor cells, it is tumorigenic in vivo, clonogenic in vitro and produces MPSV. It also secretes a colony stimulating activity (CSA), and an activity termed mixed colony promoting activity (MPA), which enables pluripotent hematopoietic stem cells to proliferate and differentiate. It differentiates through the granulomacrophage cell line independently of exogenous factors other than those which may be present in the serum.

Animals↗

Analysis of integrated proviral DNA sequences with an octadecanucleotide probe designed for specific identification of spleen focus-forming virus in the mouse genome.

The Friend spleen focus-forming virus (SFFV) is an envelope gene recombinant between the ecotropic Friend murine leukemia virus and the endogenous xenotropic mink cell focus-forming retroviral sequences. We synthesized an octadecanucleotide complementary to the 3' end of the SFFV env gene designed for discriminating the SFFV proviruses from the xenotropic mink cell focus-forming virus and ecotropic exogenous or endogenous viral sequences. Under appropriate hybridization conditions this probe allowed the identification, in addition to few endogenous DNA fragments, of multiple SFFV proviruses integrated in the genome of Friend malignant cells. Therefore this probe should be of interest in further characterizing the SFFV integration sites and possibly the SFFV ancestor gene.

Animals↗