title: A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A, activates hepatitis B virus replication.
abstract: A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A (9-HCA-A), showed potential for activating hepatitis B virus (HBV) replication. To define the mechanism of 9-HCA-A, we used HepG2 2.2.15 cells which support HBV replication. 9-HCA-A activated HBV replication, increased episomal and integrated HBV DNA content, and increased secretions of HBV antigens (HBsAg and HBeAg) into culture medium. 9-HCA-A also activated HBV transcription in Hep2 2.2.15 cell line. To examine transcriptional control mechanisms, we analyzed the effect of 9-HCA-A on four different HBV promoters (Core, PreS1, PreS2, and X) in hepatoma cell line. 9-HCA-A responsive element was located at HBx promoter. By EMSA, we showed that 9-HCA-A activated the HBx promoter by detaching the 9-HCA-A responsive element binding protein (9H-REBP). Protein phosphatase (PP2A1) treatment detaches the 9H-REBP from the HBx promoter, similar to 9-HCA-A, while protein kinase A treatment does not detach the 9H-REBP from the HBx promoter. Our results showed that 9H- REBP functions as a repressor of HBV replication while 9-HCA-A activated protein phosphatase released the BP on the HBx promoter, thus activating HBV replication.
authors.affiliation: Liver Cell Signal Transduction Laboratory, Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusong, Taejon 305-600, Republic of Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Yoon
authors.forename: In Young
authors.initials: IY
authors.lastname: Park
authors.forename: Bo Hwa
authors.initials: BH
authors.lastname: Sohn
authors.forename: Jaehyouk
authors.initials: J
authors.lastname: Lee
authors.forename: Woon Hyung
authors.initials: WH
authors.lastname: Yeo
authors.forename: Young Ik
authors.initials: YI
authors.lastname: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008847:Micromonospora / Q000737:chemistry*; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: C114119:9-hydroxycrisamicin A; D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; D014764:Viral Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases