Linked Life Data

18182442

Source:http://linkedlifedata.com/resource/pubmed/id/18182442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-4-2
pubmed:abstractText
Mutations in ZFHX1B cause Mowat-Wilson syndrome (MWS) but the precise mechanisms underlying the aberrant functions of mutant ZFHX1B proteins (also named Smad-interacting protein-1, SIP1) in patients are unknown. Using mass spectrometry analysis, we identified subunits of the NuRD corepressor complex in affinity-purified Zfhx1b complexes. We find that Zfhx1b associates with NuRD through its N-terminal domain, which contains a previously postulated NuRD interacting motif. Interestingly, this motif is substituted by an unrelated sequence in a recently described MWS patient. We show here that such aberrant ZFHX1B protein is unable to recruit NuRD subunits and displays reduced transcriptional repression activity on the XBMP4 gene promoter, a target of Zfhx1b. We further demonstrate that the NuRD component Mi-2beta is involved in repression of the Zfhx1b target gene E-cadherin as well as in Zfhx1b-induced neural induction in animal caps from Xenopus embryos. Thus, NuRD and Zfhx1b functionally interact, and defective NuRD recruitment by mutant human ZFHX1B can be a MWS-causing mechanism. This is the first study providing mechanistic insight into the aberrant function of a single domain of the multi-domain protein ZFHX1B/SIP1 in human disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1175-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18182442-Abnormalities, Multiple, pubmed-meshheading:18182442-Adenosine Triphosphatases, pubmed-meshheading:18182442-Animals, pubmed-meshheading:18182442-Autoantigens, pubmed-meshheading:18182442-Cadherins, pubmed-meshheading:18182442-Cell Line, pubmed-meshheading:18182442-DNA Helicases, pubmed-meshheading:18182442-Embryo, Nonmammalian, pubmed-meshheading:18182442-Histone Deacetylases, pubmed-meshheading:18182442-Humans, pubmed-meshheading:18182442-Intellectual Disability, pubmed-meshheading:18182442-Mi-2 Nucleosome Remodeling and Deacetylase Complex, pubmed-meshheading:18182442-Nerve Tissue Proteins, pubmed-meshheading:18182442-Protein Structure, Tertiary, pubmed-meshheading:18182442-RNA-Binding Proteins, pubmed-meshheading:18182442-Syndrome, pubmed-meshheading:18182442-Xenopus
pubmed:year
2008
pubmed:articleTitle
Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex.
pubmed:affiliation
Laboratory of Molecular Biology (Celgen), Department of Human Genetics, KULeuven, B-3000 Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't