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Z Kherrouche

Publications and source records attributed to Z Kherrouche.

4 recordsLinked to original sources

Molecular cloning and characterization of the mouse E2F6 gene.

E2F6 is the most recently identified member of the E2F family. In this study, the murine E2F6 gene was cloned and found to consist of eight exons. Analysis of its 5' flanking region revealed two transcription start sites. The proximal promoter region contained no TATA or CAAT box. We also identified a novel E2F6 mRNA containing the alternative exon 2. The E2F6 mRNAs are highly expressed during mouse embryogenesis and are present in all adult tissues examined. Moreover, E2F6 shows a unique expression pattern in synchronized mouse embryonic fibroblasts. E2F6 expression rapidly increases during the G0-G1 transition, reaching its higher level in mid-G1, and remains relatively constant thereafter. These findings suggest that E2F6 may contribute to the regulation of events throughout the cell cycle. Isolation of the murine E2F6 gene is a step toward generation of genetically modified mouse models that will help to understand the functions of E2F6.

5' Flanking Region↗

Isolation and characterization of a chicken homologue of the Spi-1/PU.1 transcription factor.

Spi-1/PU.1 is a member of the Ets family of transcription factors important in regulation of hematopoiesis. We have isolated a chicken cDNA homologuous to the mammalian Spi-1/PU.1 gene with an open reading frame of 250 amino acids (aa). The chicken Spi-1/PU.1 protein is 14 aa and 16 aa shorter than its human and mouse counterparts but is extremely well conserved with 78.8% and 75.2% identity respectively. The carboxy terminal DNA binding region, or ETS binding domain, is 100% identical to that of human and mouse. Some differences with the mammalian homologues are seen in the N-terminal part of the protein and in the PEST connecting domain. However, the differences are mainly conservative and all the features underlying functional aspects seem preserved. The major discrepancy lies in a 12 aa deletion in an already poorly conserved part of the PEST sequence. Spi-1/PU.1 transcripts were detected at high levels in spleen and Fabricius bursa of chick embryos by Northern blot and in situ hybridization. Our results show that the chicken Spi-1/PU.1 protein behaves like a bonafide Spi-1/PU.1 transcription factor in its DNA binding and transactivating properties.

Amino Acid Sequence↗

Upstream CREs participate in the basal activity of minute virus of mice promoter P4 and in its stimulation in ras-transformed cells.

The activity of the P4 promoter of the parvovirus minute virus of mice (prototype strain MVMp) is stimulated in ras-transformed FREJ4 cells compared with the parental FR3T3 line. This activation may participate in the oncolytic effect of parvoviruses, given that P4 drives a transcriptional unit encoding cytotoxic nonstructural proteins. Our results suggest that the higher transcriptional activity of promoter P4 in FREJ4 cells is mediated at least in part by upstream CRE elements. Accordingly, mutations in the CRE motifs impair P4 function more strongly in the FREJ4 derivative than in its FR3T3 parent. Further evidence that these elements contribute to hyperactivity of the P4 promoter in the ras transformant is the fact that they form distinct complexes with proteins from FREJ4 and FR3T3 cell extracts. This difference can be abolished by treating the FREJ4 cell extracts with cyclic AMP-dependent protein kinase (PKA) or treating original cultures with a PKA activator. These findings can be linked with two previously reported features of ras-transformed cells: the activation of a PKA-inhibited protein kinase cascade and the reduction of PKA-induced protein phosphorylation. In keeping with these facts, P4-directed gene expression can be up- or downmodulated in vivo by exposing cells to known inhibitors or activators of PKA, respectively.

Alkaloids↗