Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review will focus on cases of specific translational control by protein/RNA interactions in the 5'- or 3'-UTR of eukaryote mRNA where either the cis-acting RNA determinant or the trans-acting protein (or preferably both) have been identified with fair certainty. Examples of messages that are regulated by 5' motifs, which are proposed to occlude ribosome binding when bound by their specific factors, include ferritin and ribosomal protein mRNAs and the autoregulated thymidylate synthase and poly(A)-binding mRNAs. However, it has become increasingly evident recently that 3' UTR determinants and their specific binding proteins also regulate translation efficiency either directly, or indirectly via an influence on the polyadenylation status of the mRNA. It is still unclear how events at the 3' end of mRNA influence ribosome binding. Most, if not all, of the mRNAs known to be regulated by 3' UTR motifs are subject to regulation during early development or during differentiation such as several spermatocyte and oocyte mRNAs and erythroid lipoxygenase mRNA. To date, in all cases where translation is controlled directly by specific protein/mRNA interactions, the protein seems to act as a negative regulator, a translational repressor, whose binding to the specific site on the mRNA results in inhibition of initiation. The only cases of translational activation known so far concern internal initiation of translation of picornaviral RNAs, but this topic is beyond the scope of this review.
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PMID:Regulation of translation by specific protein/mRNA interactions. 788 Sep 4

The resolution phase of inflammation is being increasingly recognized as a dynamic multifaceted process whose components may be amenable to pharmacological manipulation for therapeutic gain. Here, we review evidence that the lipoxins (LX), a family of lipoxygenase-derived eicosanoids generated during cell-cell interactions within the vascular lumen, are potential endogenous inhibitors of polymorphonuclear neutrophil (PMN) recruitment during glomerular inflammation. LX are generated in nanogram quantities in kidneys of rats with Concanavalin A-ferritin (Con A-F) immune complex glomerulonephritis and of mice with acute nephrotoxic serum nephritis (NSN). PMN-platelet transcellular pathways appear to be the major route to LX formation in these settings, PMN donating the labile epoxide intermediate leukotriene A4 for conversion by platelet LX synthase to LXA4. Complementary approaches using monoclonal antibodies and gene knockout suggest that PMN-platelet adhesion through P-selectin promotes transcellular LXA4 biosynthesis in vitro and in vivo. In support of a modulatory role in PMN trafficking; LXA4 and LXB4, the LX generated in greatest quantities by mammalian cells, inhibit PMN chemotaxis, adhesion to endothelial cells, and migration across endothelium and epithelium induced leukotrienes and some other mediators in vitro. Exposure of PMN to LXA4 ex vivo attenuates their recruitment in Con A-F glomerulonephritis. Furthermore, PMN recruitment is exaggerated during NSN in P-selectin knockout mice, coincident with reduced efficiency of transcellular LXA4 generation and reduced renal LXA4 levels. Replenishment of platelet P-selectin by transfusion of null mice with wild-type platelets reverses this defect in LXA4 synthesis and approximates PMN infiltrates in null and wild-type animals. Against this background, LXA4 stable analogues have been designed that retain the biologic activity of native LXA4 in vitro and should be useful tools for probing the therapeutic potential of LXA4 in disease. In the presence of aspirin, endothelial cell cyclooxygenase II (COX-II) transforms arachidonic acid to 15R-hydroxyeicosatetraenoic acid which, in the context of PMN-endothelial cell interaction, is converted by PMN 5-lipoxygenase to 15-epi-LX. Intriguingly, these novel LX also attenuate PMN adhesion and transmigration in model in vitro systems. Together, these observations suggest that LX may not only play important regulatory roles in the "stop programs" of renal inflammation, but also contribute to the anti-inflammatory activity of aspirin and related inhibitors of COX-II.
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PMID:Lipoxins, leukocyte recruitment and the resolution phase of acute glomerulonephritis. 906 45