Human T‐cell leukemia virus type I (HTLV‐I) encodes a 40 kDa trans‐acting protein, Tax, that regulates transcription of both the proviral and cellular genes, and can transform rat fibroblasts. To determine the functional importance of its trans‐acting capacities in cell transformation, we have examined two representative pathways of transcriptional activation–HTLV‐I long terminal repeat (LTR) mediated and NF‐kappa B dependent–by mutational analysis of Tax. In contrast to a previous report, mutants lacking the ability to activate an NF‐kappaB‐dependent promoter failed to transform rat fibroblasts, whereas a mutation which abolishes the HTLV‐I LTR‐mediated trans‐activation demonstrated a wild‐type capacity for cell transformation. Stable expression of Tax competent for transformation caused enhanced DNA binding of NF‐kappa B in rat fibroblasts. We also demonstrate that stable co‐expression of the NFKB2 precursor, known as a member of the I kappa B proteins, with wild‐type Tax blocked transformation as well as eliminated aberrant NF‐kappaB activation by Tax without interference with the HTLV‐I LTR‐mediated trans‐activation. Our results indicate that constitutive activation of NF‐kappa B is essential for Tax‐mediated transformation of rat fibroblasts.
By a combination of PCR with degenerate primers and low stringency probing, we have isolated a large family of genes related to the Ca 2؉ -sensing receptor from the genome of Fugu rubripes. One of the genes (type I) is the Fugu homologue of the Ca 2؉ -sensing receptor. The remaining genes can be divided into five classes (type II-VI) on the bases of gene structure. In several types, the genes occur in clusters as tandem arrays. These genes appear to be the homologues of the vomeronasal pheromone receptors recently described in rodents. The Fugu genes are expressed in the tissues of the nose, suggesting that they may have a similar physiological role.Volatile odorants are detected by a large family of G proteincoupled receptors differentially expressed in cells of the olfactory sensory epithelium (1). The detection of pheromones is mediated through neurons of the vomeronasal organ (VNO), and a distinct class of receptors, different from the odorant receptors, was isolated by Dulac and Axel (1995) from a subset of VNO neurons (2). Very recently, three groups (3-5) have characterized a third class of G protein-coupled receptors from a different group of VNO neurons, unrelated to both classes previously found. These G protein-coupled receptors have large extracellular domains and resemble the metabotropic glutamate receptors and the Ca 2ϩ -sensing receptor. In the course of characterizing G protein-coupled receptors in the genome of the puffer fish Fugu rubripes, we encountered members of a large family of receptors related to the Ca 2ϩ -sensing receptor, which closely resemble the mammalian pheromone receptors. In this paper, we report on the characterization of these genes and show that they comprise six types, distinguished by sequence homology and gene structure. The genes occur in clusters, and we also show that they are expressed in the nose of the fish, making it likely that they are olfactory detectors.
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