Down-regulation of c-Myc and Max genes is associated to inhibition of protein phosphatase 2A in K562 human leukemia cells.
Treatment of the human myeloid leukemia K562 cells with the protein phosphatase inhibitors okadaic acid or calyculin A resulted in down-regulation of both c-myc and max genes at the mRNA and protein levels. The extent of the down-regulation was similar for both genes and was dependent on the dose and on the treatment time. Interestingly, c-myc and max down-regulation was concomitant with apoptosis induced by okadaic acid and calyculin A in K562 cells. The expression of c-myc and max returned to control levels after the removal of okadaic acid from the media, although apoptosis was irreversible. These effects were observed at okadaic acid concentrations (15 nM) that inhibited the activity of protein phosphatase type 2A but not of phosphatase type 1. We conclude that the inhibition of protein phosphatase 2A is associated to decreased levels of c-Myc/Max heterodimers in K562 cells.
D017209:Apoptosis / Q000187:drug effects; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D015152:Blotting, Northern; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology; D014176:Protein Biosynthesis; D054648:Protein Phosphatase 2; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; C499330:MAX protein, human; D008387:Marine Toxins; C067850:Myc associated factor X; D010080:Oxazoles; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D019319:Okadaic Acid; C059041:calyculin A; D054648:Protein Phosphatase 2; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases