Linked Life Data

17875642

Source:http://linkedlifedata.com/resource/pubmed/id/17875642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2007-11-12
pubmed:abstractText
Nrf2-small Maf heterodimer activates the transcription of many cytoprotective genes through the antioxidant response element and serves as a key factor in xenobiotic and oxidative stress responses. Our surface plasmon resonance-microarray binding analysis revealed that both Nrf2-MafG heterodimer and MafG homodimer bind to the consensus Maf recognition element with high affinity but bind differentially to the suboptimal binding sequences degenerated from the consensus. We examined the molecular basis distinguishing the binding profile of Nrf2-MafG heterodimer from that of MafG homodimer and found that the Ala-502 residue in the basic region of Nrf2 is a critical determinant of its binding specificity. In Maf proteins, a tyrosine resides in the position corresponding to Ala-502 in Nrf2. We prepared a mutant Nrf2 molecule in which Ala-502 was replaced with tyrosine. In surface plasmon resonance-microarray analysis, heterodimer of Nrf2(A502Y) and MafG displayed a binding specificity similar to that of MafG homodimer. The target genes activated by mutant Nrf2(A502Y)-small Maf heterodimer were largely different, albeit with some overlap, from those activated by wild-type Nrf2-small Maf, indicating that the array of target genes regulated by Nrf2-small Maf heterodimer differs substantially from that regulated by Maf homodimer in vivo. These results suggest that the distinct DNA binding profile of Nrf2-Maf heterodimer is biologically significant for Nrf2 to function as a key regulator of cytoprotective genes. Our contention is supported that the differential DNA binding specificity between Maf homodimers and Nrf2-Maf heterodimers establishes the differential gene regulation by these dimer-forming transcription factors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33681-90
pubmed:meshHeading
pubmed-meshheading:17875642-Amino Acid Sequence, pubmed-meshheading:17875642-DNA, pubmed-meshheading:17875642-Dimerization, pubmed-meshheading:17875642-Gene Expression Regulation, pubmed-meshheading:17875642-Humans, pubmed-meshheading:17875642-Kinetics, pubmed-meshheading:17875642-MafG Transcription Factor, pubmed-meshheading:17875642-Models, Molecular, pubmed-meshheading:17875642-Molecular Sequence Data, pubmed-meshheading:17875642-Mutation, pubmed-meshheading:17875642-NF-E2-Related Factor 2, pubmed-meshheading:17875642-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17875642-Protein Binding, pubmed-meshheading:17875642-Proto-Oncogene Proteins c-maf, pubmed-meshheading:17875642-Repressor Proteins, pubmed-meshheading:17875642-Sequence Homology, Amino Acid, pubmed-meshheading:17875642-Surface Plasmon Resonance, pubmed-meshheading:17875642-Tyrosine
pubmed:year
2007
pubmed:articleTitle
Molecular basis distinguishing the DNA binding profile of Nrf2-Maf heterodimer from that of Maf homodimer.
pubmed:affiliation
Graduate School of Comprehensive Human Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8572, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't