title: Transcriptional repression of E2F gene by proteasome inhibitors in human osteosarcoma cells.
abstract: E2F family of transcription factors regulates the transcription of genes required for DNA synthesis. E2F is itself controlled by a series of transcriptional and post-transcriptional pathways. Here we provide evidence that proteasome inhibitor-mediated E2F1 gene down-regulation is regulated by transcriptional events. Using the proteasome-specific inhibitors, MG132 and lactacystin, we show that the p53, the cdk inhibitors p21 and p27, and cyclin A are degraded by the ubiquitin-proteasome pathway in human osteosarcoma cells. Interestingly, the expression levels of E2F1 and E2F2 are down-regulated by proteasome inhibitors. E2F promoter and RT-PCR assay clearly demonstrated that proteasome inhibitors could reduce E2F transcriptional activation. However, MG132-induced repression of E2F1 and E2F2 is not associated with ROS generation.
authors.affiliation: Kidney Institute, School of Medicine, Keimyung University, 194 DongSan-Dong, Taegu 700-712, Republic of Korea.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Lim
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Park
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
chemical_list: D000975:Antioxidants; D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D007976:Leupeptins; D009097:Multienzyme Complexes; D014157:Transcription Factors; C063261:acetylleucyl-leucyl-norleucinal; C067713:lactacystin; D003546:Cysteine Endopeptidases; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine