The homeobox protein MSX2 interacts with tax oncoproteins and represses their transactivation activity.

Bovine leukemia virus (BLV) tax is an essential gene involved in the transcriptional activation of viral expression. Tax is also believed to be implicated in leukemogenesis because of its ability to immortalize primary cells in vitro. To gain insight into the molecular pathways mediating the activities of this important gene, we identified cellular proteins interacting with Tax. By means of a two-hybrid approach, we show that Tax specifically interacts with MSX2, a general repressor of gene expression. GST pull-down experiments and co-immunoprecipitation assays further confirmed binding specificity. Furthermore, the N-terminal residues 1-79 of MSX2 are required for binding, whereas the C-terminal residues 201-267 of MSX2 do not play a critical role. Whereas the oncogenic potential of Tax in primary cells was only slightly affected by overexpression of MSX2, the other function of Tax, namely LTR-dependent transcriptional activation, was inhibited by MSX2 in human HeLa and bovine B-lymphoblastoid (BL3) cell lines. This MSX2 repression function can be counteracted by overexpression of transcription factors CREB2 and RAP74. The Tax/MSX2 interplay thus results in repression of viral transcriptional activation possibly acting as a regulatory feedback loop. Importantly, this viral gene silencing is not strictly associated with a concomitant loss of Tax oncogenicity as measured by its ability to immortalize primary cells. And interestingly, MSX2 also interacts with and inhibits the transactivation function of the related Tax1 protein encoded by the Human T-cell leukemia virus type 1 (HTLV-1)

Régulation du métabolisme azote chez Saccharomyces Cerevisiae: aspects physiologique, biochimique, génétique et moléculaire

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression

In Saccharomyces cerevisiae, mutations at the GAP1 locus selectively abolish the activity of the general amino acid transport system. This permease catalyses active transport of apparently all biological amino acids across the plasma membrane. We have determined the nucleotide sequence of th GAP1 gene. The sequence contains an open reading frame of 601 codons corresponding to a polypeptide of M(r) 65578. This polypeptide is strongly hydrophobic; it exhibits three potential glycosylation sites. Hydropathy analysis suggests 12 membrane-spanning regions. The N-terminal domain is charged, it does not resemble hydrophobic signal sequences found in secreted proteins. Hence the GAP1 gene encodes a protein with characteristics typical of integral membrane proteins translocating ligants across cellular membranes. The deduced amino acid sequence of GAP1 protein presents strong similarities to those of the yeast arginine, histidine and proline permeases, suggesting a common evolutionary origin for these amino acid permeases. Nitrogen-source regulation of the GAP1 permease is believed to occur at two distinct levels, i.e. permease synthesis and permease activity [Grenson (1983) Eur. J. Biochem. 133, 135-139]. Northern analysis of GAP1-specific transcripts in wild-type and in mutant strains is in agreement with these views and indicates that nitrogen catabolite repression of GAP1 synthesis occurs at the RNA level.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Molecular characterization of transposable‐element‐associated mutations that lead to constitutive l‐ornithine aminotransferase expression in Saccharomyces cerevisiae

The carg B or CAR2 gene, coding for ornithine aminotransferase, was isolated by functional complementation of a carg B mutation in Saccharomyces cerevisiae. It was used as a hybridization probe to analyse RNA and chromosomal DNA from four strains bearing cis‐dominant regulatory mutations leading to constitutive, mating‐type‐dependent, ornithine aminotransferase synthesis. The four mutations appear to be insertions. Their size and restriction pattern suggested that they were transposable elements, Ty1. All were inserted in the same orientation with respect to the carg B gene. We cloned the carg B gene with its associated insertion from two constitutive mutants (carg B+Oh‐1 and carg B+Oh‐2). We determined the sequence of the carg B 5′ region from the wild‐type gene and from the two mutated genes. The DNA sequences of the extremities of the two insertions were very homologous but not identical and were similar to previously reported Ty1 element direct repeats (δ). The same five‐base‐pair sequence, ATATA, was found at both ends of both Ty1 elements, indicating that both Ty1 were transposed to the same site. This site is located 115 base pairs upstream from the putative carg B coding region. The 5′ end of carg B transcript as determined by S1 mapping was the same in the wild‐type strain and in the four mutants. The carg B transcript was not detected in the wild‐type strain grown under non‐induced conditions, while under the same conditions it was present in all four mutants. Copyright © 1987, Wiley Blackwell. All rights reservedSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Comparison of three fully implantable venous access systems. A randomized study.

Three different fully implantable venous access devices were randomly inserted in 72 patients. Comparison both from the point of view of their ease of insertion and their later use failed to show any significant difference between the three systems.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The role of the GLN3 protein carrying a GATA-A-type zinc finger in expression of the UGA4 gene of Sacharomyces cerevisiae

info:eu-repo/semantics/publishe

Expression of the ROAM mutations in Saccharomyces cerevisiae: involvement of trans-acting regulatory elements and relation with the Ty1 transcription

The regulatory mutations in Saccharomyces cerevisiae designated cargA + Oh, cargB + Oh, and durOh are alterations in the control regions of the respective structural genes. The alteration causing the cargA + Oh mutation has been shown to be an insertion of a Ty1 element in the 5' noncoding region of the CAR1 ( cargA ) locus. All three mutations cause overproduction of their corresponding gene products and belong to the ROAM family of mutations (Regulated Overproducing Allele responding to Mating signals) in yeast. The amount of overproduction in ROAM mutants is determined, at least in part, by signals that control mating functions in yeast. We report the identification of two genetic loci that regulate Oh mutant gene expression but that do not affect mating ability. These loci are defined by the recessive roc mutations ( ROAM mutation control) that reduce the amount of overproduction caused by the cargA + Oh, cargB + Oh, and durOh mutations. RNAs homologous to CAR1 ( cargA ), DUR1 ,2 and Ty1 DNA probes were analyzed by the Northern hybridization technique. In comparison with wild-type strains, cargA + Oh and durOh mutant strains grown on ammonia medium contain increased amounts of CAR1 and DUR1 ,2 RNA. This RNA overproduction is diminished in MATa/MAT alpha diploid strains as well as in haploid strains that also carry the ste7 mutation which prevents mating or that carry either of the roc1 or roc2 mutant alleles. The amount of RNA homologous to Ty1 DNA is also reduced in ste7 ,roc1 ,and roc2 mutant strains. This reduction is not observed in a strain with the ste5 mutation, which prevents mating but has no effect on overproduction of ROAM mutant gene products.(ABSTRACT TRUNCATED AT 250 WORDS)Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

A cis-dominant regulatory mutation linked to the argB-argC gene cluster in Saccharomyces cerevisiae

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Inhibition of ornithine carbamoyltransferase by arginase among yeasts: correlation with energy production, subcellular localization and enzyme synthesis

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe