Linked Life Data

17543985

Source:http://linkedlifedata.com/resource/pubmed/id/17543985

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-6-12
pubmed:abstractText
N Oct-3, a transcription factor member of the POU protein family, is implicated in normal central nervous system development but also in melanoma growth. Its DNA-binding domain (DBD) comprises two subdomains, POUs and POUh, joined by a linker peptide. We have previously shown that N Oct-3 can interact with the already described PORE and MORE DNA motifs, but also with a new structural element we have termed NORE. Having observed that both the PORE and NORE DNA-association modes depend on a strong anchoring of the POUh subdomain rigid arm into the DNA-target minor groove, in contrast to the MORE mode, we have formulated the hypothesis that phosphorylation of the conserved Ser101 residue located in the N Oct-3 POUh arm could lead to differential results in DNA binding according to the type of target. Here we demonstrate that, in vitro, Ser101 is phosphorylated by protein kinase A (PKA), either purified or contained in melanoma (624 mel) nuclear extract, and that this phosphorylation indeed significantly reduced N Oct-3 DBD binding to PORE and NORE motifs, most likely by hampering the POUh rigid arm insertion in the DNA minor groove. Conversely, no effect was observed on the binding of N Oct-3 DBD to MORE sequences. Finally, once bound to its DNA targets, N Oct-3 DBD is less susceptible to PKA activity. We conclude that transcription of genes exhibiting a MORE motif in their promoter should be less affected by N Oct-3 phosphorylation than that of genes switched on by PORE or NORE sequences.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
370
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
687-700
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17543985-Amino Acid Sequence, pubmed-meshheading:17543985-Base Sequence, pubmed-meshheading:17543985-Catalytic Domain, pubmed-meshheading:17543985-Cell Extracts, pubmed-meshheading:17543985-Cell Nucleus, pubmed-meshheading:17543985-Computer Simulation, pubmed-meshheading:17543985-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:17543985-DNA, pubmed-meshheading:17543985-Models, Molecular, pubmed-meshheading:17543985-Molecular Sequence Data, pubmed-meshheading:17543985-Mutation, pubmed-meshheading:17543985-Nucleic Acid Conformation, pubmed-meshheading:17543985-Octamer Transcription Factor-3, pubmed-meshheading:17543985-POU Domain Factors, pubmed-meshheading:17543985-Phosphorylation, pubmed-meshheading:17543985-Phosphoserine, pubmed-meshheading:17543985-Protein Binding, pubmed-meshheading:17543985-Protein Structure, Tertiary
pubmed:year
2007
pubmed:articleTitle
Differential effects of phosphorylation on DNA binding properties of N Oct-3 are dictated by protein/DNA complex structures.
pubmed:affiliation
Interactions Acides Nucléiques, Protéines Comme Cibles Pharmacologiques, Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université Paul Sabatier, Toulouse, France. laurence.nieto@ipbs.fr <laurence.nieto@ipbs.fr>
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't