Truncation does not abrogate transcriptional downregulation of the c-myc gene by sodium butyrate in Burkitt's lymphoma cells.
We have examined the effect of sodium butyrate, a potent inducer of differentiation in various cell systems, on the steady state RNA level and transcriptional activity of the c-myc gene in Burkitt's lymphoma cells. Following sodium butyrate treatment a rapid decrease of c-myc RNA was observed in all Burkitt's lymphoma cell lines studied, irrespective of the type of translocation, the location of the breakpoint relative to c-myc or of the association with EBV. Since cellular genes induced by interferon are suspected to play a role in c-myc regulation we have studied transcription of the 2-5A synthetase gene in sodium butyrate-treated Burkitt's lymphoma cells. Transcriptional activity and steady state mRNA levels of the 2-5A synthetase gene were induced by sodium butyrate. The time course of induction excluded, however, that the decrease of c-myc RNA is caused by induction of the 2-5A synthetase/RNase L endonuclease system. The reduction of c-myc RNA is caused, at least in part, by a reduced transcription rate, as shown by nuclear run-on analysis. The fact that sodium butyrate is capable of downregulating a truncated c-myc gene indicates that an important target site of transcriptional regulation is located outside the region encompassing the upstream regulatory sequences, the dual promoters and the leader region.
Abteilung für Virologie, Universität Freiburg, FRG.
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A
Polack
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Eick
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Koch
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Bornkamm
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D002051:Burkitt Lymphoma / Q000235:genetics*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D002087:Butyrates; D012333:RNA, Messenger; D020148:Butyric Acid; D015088:2',5'-Oligoadenylate Synthetase