Disease relevance of Sep15

• Unlike the E. coli enzyme, which is not a selenoprotein, the presence of selenocysteine in the mouse enzyme is indicated by a TGA codon in the open reading frame of the gene in a position corresponding to the essential cysteine of the E. coli enzyme [1].
• The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins [2].
• Measurement of selenoprotein P in human plasma has shown that it is depressed by selenium deficiency and by cirrhosis [3].
• Genetic inactivation of selenoprotein P leads to a marked reduction of brain Se content, which has not been achieved by dietary Se depletion, and to a movement disorder and spontaneous seizures [4].
• Selenoprotein P mRNA level also increased in Huh-7 human hepatoma cells incubated with GalN (5 or 10 mM) [5].

High impact information on Sep15

• SECIS elements recode UGA codons from "stop" to "sense." These RNA secondary structures, present in eukaryotic selenoprotein mRNA 3' untranslated regions, recruit a SECIS binding protein, which recruits a selenocysteine-specific elongation factor-tRNA complex [6].
• The objective of our study was to investigate the impact of overexpression of glutathione peroxidase 1 (GPX1), an intracellular selenoprotein that reduces hydrogen peroxide (H(2)O(2)) in vivo, on glucose metabolism and insulin function [7].
• Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems [8].
• Selenoprotein biosynthesis is mediated by tRNASec, which inserts selenocysteine at UGA codons in a complex, context-specific manner [9].
• Some of these genes, such as cadherin-1, selenoprotein P, platelet-activating factor acetylhydrolase, and prosaposin, had not been documented as associated with M2 [10].

Chemical compound and disease context of Sep15

• These constructions permitted high-level production of GPx mutants, where the SeCys codon was replaced by cysteine (UGC, UGU) or serine (UCA) codons, but synthesis of selenoprotein could not be detected: our data suggest that signals used for the recognition of the UGA codon as a SeCys codon are not conserved between E. coli and mammalian cells [11].

Biological context of Sep15

• The consequences on selenoprotein biosynthesis of overexpressing either the wild type or a mutant tRNA([Ser]Sec) lacking the modified base, isopentenyladenosine, in its anticodon loop were examined by introducing multiple copies of the corresponding tRNA([Ser]Sec) genes into the mouse genome [12].
• The 3-kb human SelM-encoding gene has five exons and is located on chromosome 22 but has not been correctly identified by either Celera or the public Human Genome Project. We characterized human and mouse SelM cDNA sequences and expressed the selenoprotein in various mammalian cell lines [13].
• Selenoprotein P binds to endothelial cells in the rat, and plasma levels of the protein correlate with prevention of diquat-induced lipid peroxidation and hepatic endothelial cell injury [3].
• These proteins lack common amino acid sequence motifs, but 3'-untranslated regions of selenoprotein genes contain a common stem-loop structure, selenocysteine insertion sequence (SECIS) element, that is necessary for decoding UGA as selenocysteine rather than a stop signal [14].
• Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis [3].

Anatomical context of Sep15

• Human and mouse 15-kDa selenoprotein genes manifested the highest level of expression in prostate, liver, kidney, testis, and brain, and the level of the selenoprotein was reduced substantially in a malignant prostate cell line and in hepatocarcinoma [15].
• Multiple controls over the efficiency of translation of the mRNAs encoding transition proteins, protamines, and the mitochondrial capsule selenoprotein in late spermatids in mice [16].
• (2) The mitochondrial capsule selenoprotein mRNA also initiates efficiently in vivo and in vitro, but sediments with polysomes in which the ribosomes are spaced wider than on the protamine mRNAs [16].
• Intracellular 58-kd selenoprotein levels correlate with inhibition of DNA synthesis in mammary epithelial cells [17].
• We sought to determine the selenoprotein profile of cultured human skin cells and whether selenium supplementation could protect keratinocytes and melanocytes from the lethal effects of UVB radiation [18].

Associations of Sep15 with chemical compounds

• A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose:glycoprotein glucosyltransferase [19].
• Selenoprotein P is an abundant extracellular glycoprotein that is rich in selenocysteine [3].
• Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA [20].
• The enzyme was proposed to function as a selenium delivery protein to selenophosphate synthetase in selenoprotein biosynthesis (Lacourciere, G. M., and Stadtman, T. C. (1998) J. Biol. Chem. 273, 30921-30926) [21].
• The use of the amino acids accelerated the onset of inhibition of DNA synthesis by selenite and increased the rate of actual selenoprotein synthesis [22].

Regulatory relationships of Sep15

• Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA [12].

Other interactions of Sep15

• Moreover, within affected tissues, expression of specific selenoproteins was regulated differently and often in a contrasting manner, with levels of Sep15 and the glutathione peroxidases GPx1 and GPx4 being substantially reduced [23].
• Thus, the conditional Trsp knockout mouse allows tissue-specific manipulation of Sec tRNA and selenoprotein expression, suggesting that this approach will provide a useful tool for studying the role of selenoproteins in health [23].
• We generated recombinant selenoprotein forms of TR1 and TR3 and found that these enzymes were inhibited by zinc, but not by calcium or cobalt ions [24].
• These results provide evidence that a lack of selenoprotein activity increases colon cancer susceptibility [25].
• Neither the GPX1 knockout nor the dietary Se concentrations affected mRNA levels of GPX4 in testis or selenoprotein P in kidney [26].

Analytical, diagnostic and therapeutic context of Sep15

• Sequence analysis of members of the Sep15 family identified a novel N-terminal cysteine-rich domain in Sep15 that is absent in SelM [19].
• Reverse transcriptase-polymerase chain reaction and Western blot analyses revealed that mSCL is cytosolic and predominantly exists in the liver, kidney, and testis, where mouse selenophosphate synthetase is also abundant, supporting the view that mSCL functions in cooperation with selenophosphate synthetase in selenoprotein synthesis [21].
• Real-time quantitative PCR revealed that the mRNA levels of p21(waf1), milk fat globule membrane protein E8, heat-responsive protein 12, and selenoprotein P were markedly elevated [27].
• As an initial step to evaluate the effect of selenoprotein P deletion on central nervous system architecture, the brains and cervical spinal cords of Sepp-/- and Sepp+/+ mice fed low or high selenium diets were examined by light and electron microscopy [28].
• Expression pattern of the mitochondrial capsule selenoprotein mRNA in the mouse testis after puberty; in situ hybridization study [29].

References