Source:http://linkedlifedata.com/resource/pubmed/id/14980448
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2004-2-24
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| pubmed:abstractText |
The truncated myc and max proteins, only containing basic regions and helix-loop-helix/zipper (b/HLH/Zip) regions were over-expressed in E. coli and used for the determination of the binding constant and of the inhibitory mechanism on myc-max (or max-max)-DNA complex formation. The association kinetic constants (k(1) and k(-1)) of truncated max-max or myc-max dimer and DNA were determined as k(1)=(1.7+/-0.6)x10(5) M(-1) s(-1), k(-1)=(3.4+/-1.2)x10(-2) s(-1) for max-max and DNA or k(1)=(2.1+/-0.7)x10(5) M(-1) s(-1), k(-1)=(3.2+/-1.4)x10(-2) s(-1) for myc-max and DNA. The equilibrium binding constant (K(1)) was determined using these kinetic parameters [K(XXD)=(7.8+/-2.6)x10(6) M(-1) for max-max and DNA or K(XYD)=(6.9+/-2.2)x10(6) M(-1) for myc-max and DNA]. The binding constants of myc-max or max-max dimer formation were K(XX)=(2.6+/-0.9)x10(5) M(-1) or K(XY)=(1.3+/-0.4)x10(4) M(-1), respectively. When truncated proteins were used, the max-max dimer formation was easier than the myc-max dimer formation, contrary to the physiologically determined case. This leads us to deduce that domains other than b/HLH/Zip are very important for the transcriptional regulatory activity in physiological conditions. The truncated myc and max proteins, which were expressed in E. coli and contained only b/HLH/Zip regions were also used for the screening of inhibitors of myc-max-DNA complex formation. A synthesized curcuminoid, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (curcuminoid 004), showed the most potent inhibition out of the synthesized curcuminoids, in competition with DNA. The dissociation constant of max-max dimer and the inhibitor was 9 microM, when investigated using in vitro expressed b/HLH/Zip dimer proteins. The curcuminoid 004 showed an inhibitory effect on the binding of myc-max protein to the E-box element in SNU16 cells, and suppressed the expression of myc target genes including ornithine decarboxylase (ODC), cdc25a and c-myc in myc over-expressed human stomach cancer cell line SNU16.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/Basic-Leucine Zipper Transcription...,
http://linkedlifedata.com/resource/pubmed/chemical/Curcumin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Myc associated factor X,
http://linkedlifedata.com/resource/pubmed/chemical/Nordihydroguaiaretic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Oleanolic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/momordin I (Oleanolic Acid)
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0006-3002
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
24
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| pubmed:volume |
1670
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
217-28
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:14980448-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:14980448-Basic-Leucine Zipper Transcription Factors,
pubmed-meshheading:14980448-Cell Line, Tumor,
pubmed-meshheading:14980448-Curcumin,
pubmed-meshheading:14980448-DNA-Binding Proteins,
pubmed-meshheading:14980448-Dimerization,
pubmed-meshheading:14980448-Down-Regulation,
pubmed-meshheading:14980448-E-Box Elements,
pubmed-meshheading:14980448-Escherichia coli,
pubmed-meshheading:14980448-Gene Expression Regulation,
pubmed-meshheading:14980448-Humans,
pubmed-meshheading:14980448-Kinetics,
pubmed-meshheading:14980448-Leucine Zippers,
pubmed-meshheading:14980448-Models, Molecular,
pubmed-meshheading:14980448-Molecular Structure,
pubmed-meshheading:14980448-Nordihydroguaiaretic Acid,
pubmed-meshheading:14980448-Oleanolic Acid,
pubmed-meshheading:14980448-Protein Binding,
pubmed-meshheading:14980448-Protein Structure, Tertiary,
pubmed-meshheading:14980448-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:14980448-Transcription, Genetic,
pubmed-meshheading:14980448-Transcription Factors
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| pubmed:year |
2004
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| pubmed:articleTitle |
Determination of binding constant of transcription factor myc-max/max-max and E-box DNA: the effect of inhibitors on the binding.
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| pubmed:affiliation |
Samsung Medical Center, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710, South Korea.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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