Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A homologue of IkappaBalpha, the alpha member of the IkappaB family of NF-kappaB inhibitors, was identified in a Rainbow trout suppression subtractive hybridization library enriched in sequences up-regulated in cultured leukocytes after lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFalpha) stimulation. The full-length cDNA was isolated and sequenced. The predicted amino acid sequence is 61.5% similar and 54% identical to human IkappaBalpha, while only 42% similar and 35% identical to IkappaBbeta, and 38% similar and 32% identical to IkappaBvarepsilon. Rainbow trout IkappaBalpha contains a central ankyrin repeat domain required for its interaction with NF-kappaB and a putative PEST-like sequence in the C-terminus. Expression of IkappaBalpha is up-regulated by LPS and TNFalpha treatment, two known activators of NF-kappaB, suggesting the existence of an autoregulatory loop in fish, as is the case for mammals. These results confirm the existence of the NF-kappaB signalling pathway in fish and suggest a similar functional interaction between IkappaBalpha and NF-kappaB.
...
PMID:Cloning and characterization of a homologue of the alpha inhibitor of NF-kappaB in Rainbow trout (Oncorhynchus mykiss). 1562 57

Wolbachia bacteria are endosymbiotic partners of many animal species, in which they behave as either parasites (in arthropod hosts) or mutualists (in nematode hosts). What biochemistry and biology underpin these diverse lifestyles? The recent complete sequencing of genomes from Wolbachia that infect the arthropod Drosophila melanogaster and the nematode Brugia malayi, together with the partial genome sequencing of three Wolbachia strains found in drosophilids, enables this question to begin to be addressed. Parasitic arthropod Wolbachia are characterized by the presence of phages that carry ankyrin-repeat proteins; these proteins might be exported to the host cell to manipulate reproduction. In nematode Wolbachia, which lack these phages, several biochemical pathways can deliver essential metabolites to the nematode hosts. Nematode Wolbachia might also have a role in modulating the mammalian host immune system but the sequenced Wolbachia genomes lack the genes to synthesize lipopolysaccharide, raising questions about the nature of the inducing molecule. The Wolbachia surface protein might carry out this function.
...
PMID:Wolbachia genomes: revealing the biology of parasitism and mutualism. 1640 33

Prostaglandin E2 exerts an antiinflammatory action by ligation of the heptahelical receptor EP4 in human macrophages. Because the mechanism by which EP4 receptor stimulation suppresses inflammatory activation in macrophages remains undefined, we sought interactors with the carboxyl-terminal cytoplasmic domain of the EP4 receptor. Yeast 2-hybrid screening of the human bone marrow cDNA library with the EP4 receptor as a bait identified a cDNA clone encoding a 669-amino acid protein, designated here as EP4 receptor-associated protein (EPRAP), which contains 8 ankyrin motifs that might recruit other signaling molecules. EPRAP bound to the full-length EP4 receptor in HEK293 cells cotransfected with V5-tagged EPRAP and FLAG-tagged EP4 receptor cDNA, as anti-FLAG antibody coimmunoprecipitated EPRAP with the EP4 receptor from the lysates of cotransfected cells. Human macrophages derived from peripheral blood monocytes expressed an approximately 70-kDa protein detected by Western blotting with a polyclonal anti-EPRAP antibody. Fluorescence immunohistochemistry colocalized EPRAP with the EP4 receptor in human atheromata. Interference with EPRAP function by small interference RNA limited prostaglandin E2-mediated suppression of chemokine expression in macrophages activated with lipopolysaccharide and tumor necrosis factor alpha. In conclusion, the antiinflammatory action of prostaglandin E2 in macrophages involves EPRAP that associates directly with the cytoplasmic tail of EP4 receptor.
...
PMID:A novel prostaglandin E receptor 4-associated protein participates in antiinflammatory signaling. 1642 69

A novel member of the IkappaB family, human IkappaB-zeta, was identified by a differential screening approach of apoptosis-sensitive and -resistant tumor cells. The protein consists of 6 ankyrin repeats at its COOH terminus and shares about 30% identity with other IkappaB members. IkappaB-zeta associates with both the p65 and p50 subunit of NF-kappaB and inhibits the transcriptional activity as well as the DNA binding of the transcription factor. Interestingly, IkappaB-zeta is localized in the nucleus where it aggregates in matrix-associated deacetylase bodies, indicating that IkappaB-zeta regulates nuclear NF-kappaB activity rather than its nuclear translocation from the cytoplasm. IkappaB-zeta expression itself was regulated by NF-kappaB, suggesting that its activity is controlled in a negative feedback loop. Unlike classical IkappaB proteins, IkappaB-zeta was not degraded upon cell stimulation. Treatment with tumor necrosis factor-alpha, interleukin-1beta, and lipopolysaccharide induced a strong induction of IkappaB-zeta transcripts. Expression of IkappaB-zeta was detected in different tissues including lung, liver, and in leukocytes but not in the brain. Suppression of endogenous IkappaB-zeta by RNA interference rendered cells more resistant to apoptosis, whereas overexpression of IkappaB-zeta was sufficient to induce cell death. Our results, therefore, suggest that IkappaB-zeta functions as an additional regulator of NF-kappaB activity and, hence, provides another control level for the activation of NF-kappaB-dependent target genes.
...
PMID:A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding. 1651 45

Ichnoviruses (IVs) occur in obligate symbiotic associations with endoparasitic ichneumonid wasps. IVs are injected with eggs during parasitization, where viral infection and gene expression alter host physiology to ensure endoparasitoid survival. The seven Campoletis sonorensis IV (CsIV) vankyrin genes encode proteins that possess ankyrin repeat domains resembling the inhibitory domains of NF-kappaB transcription factor inhibitors (IkappaBs). The CsIV vankyrins are divided into two subclasses: those expressed primarily in the host fat body (three genes) and those expressed in host hemocytes (four genes). CsIV vankyrin proteins showed limited antigenic similarity when analyzed by Western blotting. Cellular localization and expression patterns of recombinant vankyrin proteins in High Five and Sf9 insect cells differed within and between the subclasses and in cells exposed to lipopolysaccharide, laminarin, or viral immune challenge. In unstimulated Sf9 cells, five vankyrins were detected in cell nuclei. The remaining two proteins localized predominantly to cytoplasmic granules. Immune stimulation of cells resulted in a nuclear-to-cytoplasmic shift of three vankyrins but did not affect localization of other variants. When expressed from recombinant Autographa californica multiple nucleopolyhedroviruses (AcMNPVs), all vankyrins showed a nuclear localization during early stages of infection with patterns resembling those of immune-challenged cells as the infection progressed. Two fat body vankyrins also produced unique biological effects when expressed from recombinant AcMNPV. Insect cells infected with these viruses exhibited enhanced longevity compared to those infected with viruses expressing other vankyrins. Together, these data suggest that vankyrin proteins in CsIV have divergent physiological functions.
...
PMID:Divergences in protein activity and cellular localization within the Campoletis sonorensis Ichnovirus Vankyrin family. 1700 54

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is a nuclear IkappaB protein that is also known as interleukin-1-inducible nuclear ankyrin repeat protein and inhibitor of nuclear factor kappaBzeta (IkappaBzeta). We previously observed that MAIL-deficient mice were affected by atopic dermatitis-like skin lesions and demonstrated the importance of MAIL in the skin. In this study, we investigated MAIL expression in mouse keratinocytes. MAIL mRNA was constitutively expressed in the skin epidermis. MAIL expression was also confirmed in primary keratinocytes and the PAM212 keratinocyte cell line. The inhibitors of nuclear factor kappaB (NF-kappaB)-Bay11-7082 and the IkappaBalphaM supersuppressor-considerably downregulated MAIL expression in the keratinocytes. Immunoreactivity for NF-kappaB components was localized in the cytoplasm and nucleus of normal unstimulated keratinocytes. The expression level of MAIL in the skin did not change following lipopolysaccharide (LPS) administration to mice. Interestingly, in accordance with the in vivo findings, the MAIL expression level did not change following LPS stimulation even in primary keratinocytes; however, MAIL expression was strongly increased by interleukin-1 stimulation. These results collectively suggest that the constitutive expression of MAIL in keratinocytes is controlled, at least in part, by NF-kappaB and that there may be LPS-specific repressive mechanisms that inhibit MAIL induction.
...
PMID:Role of NF-kappaB in constitutive expression of MAIL in epidermal keratinocytes. 1740 44

We identified and characterized the Japanese flounder (Paralichthys olivaceus) inhibitor kappa B alpha (JFIKBA) cDNA. The JFIKBA cDNA contains an open reading frame of 960bp encoding 320 amino acid residues. JFIKBA contains 6 ankyrin repeats in the central coding region. Expression studies by RT-PCR showed constitutive expression of the JFIKBA gene in several Japanese flounder tissues (brain, muscle, gill, heart, kidney, liver, spleen and intestine). Moreover, expression of JFIKBA mRNA was induced in kidney by LPS stimulation. To investigate the role of JFIKBA, we constructed a recombinant plasmid expressing the JFIKBA coding region under the control of the cytomegalovirus (CMV) promoter. Over-expression of the JFIKBA gene in the Japanese flounder cultured cell line derived from kidney, suppressed the expression of the TNF alpha gene with lipopolysaccharide stimulation. These results indicated that JFIKBA has an important role in the innate immune system, especially in the signaling of the cytokine network.
...
PMID:Cloning and characterization of the IkappaBalpha gene from Japanese flounder, Paralichthys olivaceus. 1747

Macrophage activation participates pivotally in the pathophysiology of chronic inflammatory diseases, including atherosclerosis. Through the receptor EP4, prostaglandin E(2) (PGE(2)) exerts an anti-inflammatory action in macrophages, suppressing stimulus-induced expression of certain proinflammatory genes, including chemokines. We recently identified a novel EP4 receptor-associated protein (EPRAP), whose function in PGE(2)-mediated anti-inflammation remains undefined. Here we demonstrate that PGE(2) pretreatment selectively inhibits lipopolysaccharide (LPS)-induced nuclear factor kappaB1 (NF-kappaB1) p105 phosphorylation and degradation in mouse bone marrow-derived macrophages through EP4-dependent mechanisms. Similarly, directed EPRAP expression in RAW264.7 cells suppresses LPS-induced p105 phosphorylation and degradation, and subsequent activation of mitogen-activated protein kinase kinase 1/2. Forced expression of EPRAP also inhibits NF-kappaB activation induced by various proinflammatory stimuli in a concentration-dependent manner. In co-transfected cells, EPRAP, which contains multiple ankyrin repeat motifs, directly interacts with NF-kappaB1 p105/p50 and forms a complex with EP4. In EP4-overexpressing cells, PGE(2) enhances the protective action of EPRAP against stimulus-induced p105 phosphorylation, whereas EPRAP silencing in RAW264.7 cells impairs the inhibitory effect of PGE(2)-EP4 signaling on LPS-induced p105 phosphorylation. Additionally, EPRAP knockdown as well as deficiency of NF-kappaB1 in macrophages attenuates the inhibitory effect of PGE(2) on LPS-induced MIP-1beta production. Thus, PGE(2)-EP4 signaling augments NF-kappaB1 p105 protein stability through EPRAP after proinflammatory stimulation, limiting macrophage activation.
...
PMID:Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation. 1827 Feb 4

Nucling is an Apaf1-binding proapoptotic protein involved in apoptosome-mediated apoptosis. Luciferase assays have revealed that the activation of nuclear factor-kappaB induced by tumor necrosis factor-alpha, interleukin-1beta and lipopolysaccharide is downregulated by the overexpression of Nucling in HEK293 cells. Moreover, the expression of endogenous cyclooxygenase 2, tumor necrosis factor-alpha and galectin-3, the end-point molecules in the pathway for the activation of nuclear factor-kappaB, as well as nuclear factor-kappaB (p65) itself, is upregulated in Nucling gene-deficient mouse embryonic fibroblasts, suggesting that nuclear factor-kappaB is a target of Nucling. Subsequent study has revealed that Nucling physically interacts with nuclear factor-kappaB (p65 and p50) and that the binding domain of Nucling is its amino-terminal region (amino acids 1-466) containing ankyrin repeats. Overexpression of Nucling prevents the translocation of nuclear factor-kappaB into the nucleus. In addition, the cytoplasmic retention of endogenous nuclear factor-kappaB in resting cells is not observed in Nucling gene-deficient mouse embryonic fibroblasts. These results reveal a novel function of Nucling as a suppressor of nuclear factor-kappaB, mediated by its cytoplasmic retention through physical interaction.
...
PMID:Nucling interacts with nuclear factor-kappaB, regulating its cellular distribution. 1918 22

The peripheral membrane protein, protein 4.2, is one of the most abundant protein components of the erythrocyte membrane. Protein 4.2 has an important role in red cell membrane structure, its absence due to natural mutations in humans or gene knockout in mice has a detrimental effect on membrane stability and results in hereditary spherocytosis. It is known to be a point of connection between the band 3 complex and the Rhesus protein complex, through its associations with band 3 and CD47 and also via interactions with the cytoskeletal protein ankyrin. Considering its relatively high abundance and importance in stability of the erythrocyte membrane, protein 4.2 has proved a somewhat neglected protein in recent years. In this review we will summarize our current understanding of protein 4.2, discuss its known interactions and describe the effects and implications of protein 4.2 deficiency. Based on protein 4.2's close homology with transglutaminase family proteins, we propose a new speculative "open" homology structure for protein 4.2 that may represent the active, membrane associated protein 4.2 molecule in red blood cells and also explain the dependence of protein 4.2 on band 3 binding for stability.
...
PMID:Protein 4.2: a complex linker. 1926


<< Previous 1 2 3 Next >>

---