Transcriptional repression of E2F gene by proteasome inhibitors in human osteosarcoma cells.
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.
Lim
Jun Hee
JH
Kidney Institute, School of Medicine, Keimyung University, 194 DongSan-Dong, Taegu 700-712, Republic of Korea.
Chang
Young-Chae
YC
Park
Yong Bok
YB
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
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
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