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http://purl.uniprot.org/citations/20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20668023http://www.w3.org/2000/01/rdf-schema#comment"Aromatase, a key enzyme of estrogen biosynthesis, is transcriptionally regulated by many growth factors. IGF-I enhances aromatase activity in a variety of cells, but the mechanism of action has not been determined. We herein report our finding of a novel mechanism of action for IGF-I. IGF-I enhanced the dexamethasone (DEX)-induced aromatase activity by 30% in serum-starved THP-1 cells. The increase was associated with a corresponding increase in the level of aromatase protein but not with any change in the mRNA level. Metabolic labeling experiments revealed that IGF-I inhibited the degradation of aromatase. We identified pepstatin A as the most effective inhibitor of aromatase degradation by in vitro assay. Using a nontoxic concentration of pepstatin A, we examined IGF-I's action on aromatase distribution in microsomes and lysosomes. In the presence of pepstatin A, DEX caused an increase in the amount of aromatase in both microsomes and lysosomes, and IGF-I attenuated the DEX-induced accumulation of aromatase in lysosomes and, conversely, enhanced its accumulation in the microsomes. The addition of serum abolished the IGF-I-induced changes. The transport from microsome to lysosome was fluorescently traced in cells using a recombinant aromatase. IGF-I selectively reduced the aromatase signal in the lysosomes. Finally, we observed that IGF-I enhanced the aromatase activity by 50% as early as 1 h after treatment; furthermore, rapamycin, an enhancer of autophagy, completely negated the effect of IGF-I on the enzyme. These results indicate that IGF-I enhances aromatase by the inhibition of autophagy."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.org/dc/terms/identifier"doi:10.1210/en.2010-0294"xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Ishikawa H."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Inoue M."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Murakami K."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Nomura K."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Okada M."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Zhang B."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Kasai T."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Harada N."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/author"Shozu M."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/name"Endocrinology"xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/pages"4949-4958"xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/title"Insulin-like growth factor I enhances the expression of aromatase P450 by inhibiting autophagy."xsd:string
http://purl.uniprot.org/citations/20668023http://purl.uniprot.org/core/volume"151"xsd:string
http://purl.uniprot.org/citations/20668023http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20668023
http://purl.uniprot.org/citations/20668023http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20668023
http://purl.uniprot.org/uniprot/#_A8K6W3-mappedCitation-20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20668023
http://purl.uniprot.org/uniprot/#_Q16449-mappedCitation-20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20668023
http://purl.uniprot.org/uniprot/#_Q16481-mappedCitation-20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20668023
http://purl.uniprot.org/uniprot/#_P11511-mappedCitation-20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20668023
http://purl.uniprot.org/uniprot/#_Q8IYG4-mappedCitation-20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20668023
http://purl.uniprot.org/uniprot/#_Q05CU4-mappedCitation-20668023http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20668023