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http://purl.uniprot.org/citations/10421424http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10421424http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10421424http://www.w3.org/2000/01/rdf-schema#comment"Hypothemycin was originally isolated as an antifungal metabolite of Hypomyces trichothecoides. Here we report that treatment on v-K-ras-transformed NIH3T3 cells (DT cells) with hypothemycin caused drastic decrease in amount of cyclin D1 protein with concomitant prolongation of G1 phase in their cell cycle. Analysis using hypothemycin-resistant mutant of Schizosaccharomyces pombe (S. pombe) was carried out to show that S. pombe rhp6+ (homologue of Saccharomyces cerevisiae RAD6) and mammalian ubiquitin-conjugating enzyme 2 (ubc2) are the targets of hypothemycin or its downstream molecules in ubiquitin-conjugation process. Furthermore, in the presence of lactacystin, a specific inhibitor for proteasome, hypothemycin greatly enhanced the accumulation of multi-ubiquitinated form of cyclin D1 in DT cells. Therefore, it is indicated that hypothemycin facilitates ubiquitinating process of cyclin D1. In terms of malignant phenotype, hypothemycin inhibited anchorage-independent growth and reverted the morphology of DT cells. On the contrary, their morphology still remained transformed in the additional presence of lactacystin. Our results suggest that cyclin D1 is a key molecule working downstream in ras-signaling and that the transformation can be inhibited by the compound which can activate ubiquitin-proteasome pathway including degradation of cyclin D1."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.org/dc/terms/identifier"doi:10.1016/s0024-3205(99)00259-3"xsd:string
http://purl.uniprot.org/citations/10421424http://purl.org/dc/terms/identifier"doi:10.1016/s0024-3205(99)00259-3"xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Nishida K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Nishida K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Omura S."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Omura S."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Hojo K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Hojo K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Sonoda H."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Sonoda H."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Omi K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Omi K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Sugita K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/author"Sugita K."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/name"Life Sci."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/name"Life Sci."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/pages"381-394"xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/pages"381-394"xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/title"Suppression of oncogenic transformation by hypothemycin associated with accelerated cyclin D1 degradation through ubiquitin-proteasome pathway."xsd:string
http://purl.uniprot.org/citations/10421424http://purl.uniprot.org/core/title"Suppression of oncogenic transformation by hypothemycin associated with accelerated cyclin D1 degradation through ubiquitin-proteasome pathway."xsd:string