Unsaturated fatty acids bind Myc-Max transcription factor and inhibit Myc-Max-DNA complex formation.
Oncoprotein Myc, hetero-dimerized with Max through a b/HLH/Zip region, is a transcription factor that governs important cellular processes such as cell cycle entry, proliferation and differentiation. We found that linoleic acid, isolated from Pollen Typhae, and other unsaturated fatty acids have strong inhibitory effects on the binding of Myc-Max heterodimer to an E-box DNA site (CA(C/T)GTG). The interaction of a fatty acid with a protein dimer, not with DNA, is assumed to block the entire Myc-Max-DNA complex formation. Unsaturated fatty acids also showed cytotoxicity against a SNU16 human stomach cancer cell line and conjugated linoleic acid suppressed mRNA expression of several myc-target genes; ornithine decarboxylase, p53, cdc25a in the SNU16 cells.
Chung
Sunah
S
School of Chemistry and Molecular Engineering, Seoul National University, 151-742, Seoul, South Korea.
Park
Seyeon
S
Yang
Chul Hak
CH
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001667:Binding, Competitive; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; C499330:MAX protein, human; C067850:Myc associated factor X; D065108:Ornithine Decarboxylase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D009955:Ornithine Decarboxylase; C022616:thiazolyl blue