Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A putative growth hormone receptor from detergent-solubilized rabbit liver membranes and the growth hormone binding protein from rabbit serum have been purified 59,000- and 400,000-fold, respectively, primarily by affinity chromatography. Both purified proteins exhibit high affinity binding for human growth hormone; K alpha = 9-30 x 10(9) M-1 for the liver receptor and K alpha = 6 x 10(9) M-1 for the binding protein. The apparent molecular weight of the liver receptor is 130,000 by reduced sodium dodecyl sulfate gel electrophoresis, while that of the binding protein is 51,000. Both contain N-linked carbohydrate. The amino-terminal sequences of the liver growth hormone receptor and the serum binding protein were found to be the same, indicating that the binding protein corresponds to the extracellular domain of the liver receptor. Ubiquitin was found covalently linked to the liver receptor but not to the serum binding protein. The amino acid sequences of several peptides from the liver receptor were also determined after tryptic and V8 protease digestion.
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PMID:Rabbit liver growth hormone receptor and serum binding protein. Purification, characterization, and sequence. 337 9

We determined the effects of 24-h recombinant human growth hormone (rhGH) infusion into a femoral artery on leg muscle protein kinetics, amino acid transport, and glutamine metabolism in eight adult hypercatabolic trauma patients. Metabolic pathways were assessed by leg arteriovenous catheterization and muscle biopsies with the use of stable amino acid isotopes. Muscle mRNA levels of selected enzymes were determined by competitive PCR. rhGH infusion significantly accelerated the inward transport rates of phenylalanine and leucine and protein synthesis, whereas the muscle protein degradation rate and cathepsin B and UbB polyubiquitin mRNA levels were not significantly modified by rhGH. rhGH infusion decreased the rate of glutamine de novo synthesis and glutamine precursor availability, total branched-chain amino acid catabolism, and nonprotein glutamate utilization. Thus net glutamine release from muscle into circulation significantly decreased after rhGH administration ( approximately 50%), whereas glutamine synthetase mRNA levels increased after rhGH infusion, possibly to compensate for reduced glutamine precursor availability. We conclude that, after trauma, the anticatabolic action of rhGH is associated with a potentially harmful decrease in muscle glutamine production.
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PMID:Growth hormone decreases muscle glutamine production and stimulates protein synthesis in hypercatabolic patients. 1091 32

Insulin-like growth factor I (IGF-I) and growth hormone (GH) exert their anabolic actions by increasing protein synthesis, but only IGF-I has been reported to impede protein breakdown. Using a model of myofibrillar catabolism produced by dexamethasone (Dex) we have reported that IGF-I down-regulates Dex-induced mRNAs for Ubiquitin (Ub) and Ub-conjugating enzymes (E2) in skeletal muscle, whereas GH had no significant effect. In the present study, we used the same model to determine whether IGF-I (0.35 mg/100 g BW) and/or GH (0.3 mg/100 g BW) have effects on proteasome subunit mRNAs in skeletal muscles of rats treated with Dex (0.5 mg/100 g BW) for 3 days. Dex caused significant increases in C-2, -3, and -8 proteasome subunit mRNAs (6.0-, 4.0-, and 6.6-fold increases, respectively). Injections of IGF-I in Dex-treated animals caused significant suppression of transcripts for C-2, -3, and -8 (32%, 42%, and 40%, respectively). GH restored the serum IGF-I levels in Dex treated animals, but caused further increases in proteasome subunit mRNAs (C-2, 35%; C-3, 34.5%; C-8, 33%; C-6, 42%; C-5, 32%; C-9, 37%). Administration of IGF-I in the Dex/GH-treated animals decreased the mRNAs of proteasome subunits in a manner and degree similar to those observed in the Dex/IGF-I group. Surprisingly, injection of GH alone in normal animals increased proteasome subunit mRNAs in skeletal muscle (C-2, 85%; C-3, 109%; C-8, 91%). This effect of GH on proteasome subunit mRNAs was also observed in liver. These findings suggest, therefore, that suppression of Dex-induced expression of proteasome subunit mRNAs in skeletal muscle is one of the mechanisms by which IGF-I exerts its antiproteolytic activity in catabolic states. On the other hand, the biological function of GH in regulating proteasome subunits needs further investigation.
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PMID:Divergent regulation of proteasomes by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone. 1242 29

Efficient and prolonged human cystic fibrosis transmembrane conductance regulator (hCFTR) expression is a major goal for cystic fibrosis (CF) lung therapy. A hCFTR expression plasmid was optimized as a payload for compacted DNA nanoparticles formulated with polyethylene glycol (PEG)-substituted 30-mer lysine peptides. A codon-optimized and CpG-reduced hCFTR synthetic gene (CO-CFTR) was placed in a polyubiquitin C expression plasmid. Compared to hCFTR complementary DNA (cDNA), CO-CFTR produced a ninefold increased level of hCFTR protein in transfected HEK293 cells and, when compacted as DNA nanoparticles, produced a similar improvement in lung mRNA expression in Balb/c and fatty acid binding protein promoter (FABP) CF mice, although expression duration was transient. Various vector modifications were tested to extend duration of CO-CFTR expression. A novel prolonged expression (PE) element derived from the bovine growth hormone (BGH) gene 3' flanking sequence produced prolonged expression of CO-CFTR mRNA at biologically relevant levels. A time course study in the mouse lung revealed that CO-CFTR mRNA did not change significantly, with CO-CFTR/mCFTR geometric mean ratios of 94% on day 2, 71% on day 14, 53% on day 30, and 14% on day 59. Prolonged CO-CFTR expression is dependent on the orientation of the PE element and its transcription, is not specific to the UbC promoter, and is less dependent on other vector backbone elements.
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PMID:Optimization of hCFTR lung expression in mice using DNA nanoparticles. 2195 68