Functional characterization of human cysteinyl leukotriene 1 receptor gene structure.

The 5-lipoxygenase pathway has been strongly implicated in the pathogenesis of chronic inflammatory disorders, such as bronchial asthma and atherosclerosis. Cysteinyl leukotrienes (cysLTs), 5-lipoxygenase pathway products, are recognized now not only as important factors in asthmatic inflammation, but also as mediators of cell trafficking and innate immune responses. To study a role of cysLTs in inflammatory reactions we have characterized the gene structure of human cysteinyl leukotriene receptor type I (cysLT(1)R).

The role of TFIID, the initiator element and a novel 5' TFIID binding site in the transcriptional control of the TATA-less human cytosolic phospholipase A2-alpha promoter.

Human cytosolic phospholipase A2-alpha (cPLA2-alpha) is a critical enzyme in the liberation of arachidonic acid (AA) from cellular membranes and the subsequent formation of prostaglandins (PGs), leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs) and platelet activating factor in many different cell types. Much is known of the effect of posttranslational phosphorylation and calcium binding events on the enzymatic activity of cPLA2-alpha, but to date little is known about its specific transcriptional control. Through the use of reporter gene constructs and eletrophoretic mobility shift assays (EMSAs), this study determined the minimal promoter required for basal transcriptional activity of the human cPLA2-alpha promoter to include base pairs -40 through the transcription start site (TSS).

Characterization of the human p11 promoter sequence.

p11 is expressed in many different cell types, and serves a variety of regulatory functions. In order to better understand the transcriptional control of this protein, the 5' promoter region of the human p11 gene was cloned and sequenced. After confirming the transcription start point (TSP) using 5' rapid amplification of cDNA ends analysis, the 5' promoter was analysed.

Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding.

Proteolytic cleavage of TNF receptor 1 (TNFR1) generates soluble receptors that regulate TNF bioactivity. We hypothesized that the mechanism of TNFR1 shedding might involve interactions with regulatory ectoproteins. Using a yeast two-hybrid approach, we identified ARTS-1 (aminopeptidase regulator of TNFR1 shedding) as a type II integral membrane protein that binds to the TNFR1 extracellular domain.