Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteasome is a large multisubunit complex involved in intracellular proteolysis in antigen processing for loading MHC class I molecules. Two activators PA28-alpha and PA28-beta, which are induced by interferon-gamma (IFN-gamma), activate this latent enzyme complex. Genes encoding these activators, PSME1 and PSME2, respectively, have been characterized from various mammalian but only from zebrafish among piscine. We have cloned a PSME2 gene homologue from a leukocyte cDNA library of flounder, a marine fish. The flounder PSME2 gene (fPSME2) encompasses 1063 nucleotides and encodes a polypeptide of 242 amino acids (aa), with a deduced molecular weight of 27.2 kDa. The deduced protein has 82% sequence similarity to that of zebrafish and 73-74% sequence similarity to that of various mammalians and shows higher level sequence homology in the C-terminal region. There was a PA28-beta protein subunit-specific insert located at the corresponding to the KEKE motif of PA28-alpha protein. A phylogenetic tree derived using deduced amino acid sequences showed a diversion of piscine PSME2 from mammalian counterpart after diversion of PSME1 and PSME2 from a common ancestral gene. Northern blot analysis revealed a higher level expression of fPSME2 gene in kidney, spleen and muscle tissues of bacterial lipopolysaccharide (LPS) stimulated flounder than those from non-induced flounder.
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PMID:Cloning and sequence analysis of cDNA for the proteasome activator PA28-beta subunit of flounder (Paralichthys olivaceus). 1459 64

The effects of cortisol (CORT) on resting and lipopolysaccharide (LPS)-activated monocyte-derived THP-1 macrophages were investigated by proteomics. Forty-seven proteins were found to be modulated, 20 by CORT, 11 by LPS, and 16 by CORT and LPS. Cortisol-sensitive chaperones and cytoskeletal proteins were mostly repressed. HCLS1, MGN, and MX1 were new proteins identified to be under the transcriptional control of this steroid and new CORT-sensitive variants of MX1, SYWC and IFIT3 were found. FKBP51, a known CORT target gene, showed the strongest response to CORT and synergism with LPS. In resting THP-1 macrophages, 18 proteins were modulated by CORT, with 15 being down-regulated. Activation of macrophages by LPS was associated with enhanced expression of immune response and metabolic proteins. In activated macrophages, CORT had a more equilibrated effect and almost all metabolism-related proteins were up-regulated, whereas immune response proteins were mostly down-regulated. The majority of the LPS up-regulated immune response-related proteins are known interferon (IFN) target genes (IFIT3, MX1, SYWC, PSME2) suggesting activation of the IRF3 signaling pathway. They were all suppressed by CORT. This is the first proteomics study to investigate the effects of CORT on activated immune cells.
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PMID:Cortisol is a potent modulator of lipopolysaccharide-induced interferon signaling in macrophages. 2050 17