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Identification of microbial metabolites that accelerate the ubiquitindependent degradation of c-Myc 被引量:1
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作者 ZIYU LIU AKIKO OKANO +8 位作者 EMIKO SANADA yushi futamura TOSHIHIKO NOGAWA KOSUKE ISHIKAWA KENTARO SEMBA JIANG LI XIAOMENG LI HIROYUKI OSADA NOBUMOTO WATANABE 《Oncology Research》 SCIE 2023年第5期655-666,共12页
Myc belongs to a family of proto-oncogenes that encode transcription factors.The overexpression of c-Myc causes many types of cancers.Recently,we established a system for screening c-Myc inhibitors and identified anti... Myc belongs to a family of proto-oncogenes that encode transcription factors.The overexpression of c-Myc causes many types of cancers.Recently,we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library.The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained.In this study,we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp.RK19-A0402 strongly inhibits c-Myc transcriptional activity.After purification of the hit broth,we identified compounds closely related to the aglycone of cytovaricin and had a structure similar to that of oligomycin A.Similar to oligomycin A,the hit compounds inhibited mitochondrial complex V.The mitochondria dysfunction caused by the compounds induced the production of reactive oxygen species(ROS),and the ROS activated GSK3α/βthat phosphorylated c-Myc for ubiquitination.This study provides a successful screening strategy for identifying natural products as potential c-Myc inhibitors as potential anticancer agents. 展开更多
关键词 High-throughput screening PHOSPHORYLATION Reactive oxygen species
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