Linked Life Data

12519782

Source:http://linkedlifedata.com/resource/pubmed/id/12519782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2003-3-24
pubmed:abstractText
Nuclear receptors mediate gene activation through ligand-dependent interaction with coactivators. We previously cloned and characterized thyroid hormone receptor-binding protein, TRBP (NcoA6: AIB3/ASC-2/RAP250/PRIP/TRBP/NRC), as an LXXLL-containing coactivator that associates with coactivator complexes through its C terminus. To search for protein factors involved in TRBP action, we identified a distinct set of proteins from HeLa nuclear extract that interacts with the C terminus of TRBP. Analysis by mass spectrometric protein sequencing revealed a DNA-dependent protein kinase (DNA-PK) complex including its catalytic subunit and regulatory subunits, Ku70 and Ku86. DNA-PK is a heterotrimeric nuclear phosphatidylinositol 3-kinase that functions in DNA repair, recombination, and transcriptional regulation. DNA-PK phosphorylates TRBP at its C-terminal region, which directly interacts with Ku70 but not Ku86 in vitro. In addition, in the absence of DNA, TRBP itself activates DNA-PK, and the TRBP-stimulated DNA-PK activity has an altered phosphorylation pattern from DNA-stimulated activity. An anti-TRBP antibody inhibits TRBP-induced kinase activity, suggesting that protein content of TRBP is responsible for the stimulation of DNA-independent kinase activity. Furthermore, in DNA-PK-deficient scid cells, TRBP-mediated transactivation is significantly impaired, and nuclear localization of TRBP is altered. The activation of DNA-PK in the absence of DNA ends by the coactivator TRBP suggests a novel mechanism of coactivator-stimulated DNA-PK phosphorylation in transcriptional regulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11471-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12519782-Carrier Proteins, pubmed-meshheading:12519782-DNA-Activated Protein Kinase, pubmed-meshheading:12519782-DNA-Binding Proteins, pubmed-meshheading:12519782-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12519782-Enzyme Activation, pubmed-meshheading:12519782-Fluorescent Antibody Technique, pubmed-meshheading:12519782-HeLa Cells, pubmed-meshheading:12519782-Humans, pubmed-meshheading:12519782-Membrane Proteins, pubmed-meshheading:12519782-Nuclear Proteins, pubmed-meshheading:12519782-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12519782-Phosphorylation, pubmed-meshheading:12519782-Protein Binding, pubmed-meshheading:12519782-Protein-Serine-Threonine Kinases, pubmed-meshheading:12519782-Recombination, Genetic, pubmed-meshheading:12519782-Substrate Specificity, pubmed-meshheading:12519782-Thyroid Hormones, pubmed-meshheading:12519782-Transcription, Genetic
pubmed:year
2003
pubmed:articleTitle
Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase.
pubmed:affiliation
Department of Gene Regulation, Bone and Inflammation Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. kol@lilly.com
pubmed:publicationType
Journal Article