Linked Life Data

8968743

Source:http://linkedlifedata.com/resource/pubmed/id/8968743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-3-14
pubmed:abstractText
Craniosynostosis, Boston type is an autosomal dominant disorder that results in the premature fusion of calvarial bones and ensuing abnormalities in skull shape. We showed previously that this disorder is tightly linked to the Msx2 homeobox gene on the long arm of chromosome 5, and that affected individuals bear a mutated copy of Msx2. In addition, transgenic mice in which either mutant or wild-type mouse Msx2 is overexpressed in the developing skull also exhibit craniosynostosis. That both mutant and wild-type Msx2 elicit craniosynostosis in transgenic mice and that the Boston type mutation is dominant led us to hypothesize that the mutation might enhance the normal function of Msx2. The mutation is located in position 7 of the N-terminal arm of the homeodomain, a region implicated in both target sequence recognition and protein-protein interactions. Here we test the hypothesis that the Pro148-->His mutation alters the DNA binding properties of Msx2. Using gel shift and binding site selection analyses, we show that the mutation enhances the affinity of Msx2 for a set of known Msx2 target sequences but has little or no effect on the site specificity of Msx2 binding. The enhancement of Msx2 binding is due largely if not entirely to an increased stability of the mutant Msx2-DNA complex. These data provide a molecular-level explanation of how the Pro148-->His mutation enhances Msx2 function and thus leads to the dominant craniosynostosis phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1915-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Kenneth R. Norris Cancer Hospital, Los Angeles, CA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.