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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2005-9-26
pubmed:abstractText
Checkpoint Suppressor 1 (CHES1; FOXN3) encodes a member of the forkhead/winged-helix transcription factor family. The human CHES1 cDNA was originally identified by its ability to function as a high-copy suppressor of multiple checkpoint mutants of Saccharomyces cerevisiae. Accumulating expression profile data suggest that CHES1 plays a role in tumorigenicity and responses to cancer treatments, though nothing is known regarding the transcriptional function of CHES1 or other FOXN proteins in human cells. In this report, we find that the carboxyl terminus of CHES1 fused to a heterologous DNA binding domain consistently represses reporter gene transcription in cell lines derived from tumor tissues. Using a cytoplasmic two-hybrid screening approach, we find that this portion of CHES1 interacts with Ski-interacting protein (SKIP; NCoA-62), which is a transcriptional co-regulator known to associate with repressor complexes. We verify this interaction through co-immunoprecipitation experiments performed in mammalian cells. Further analysis of the CHES1/SKIP interaction indicates that CHES1 binds to a region within the final 66 hydrophobic residues of SKIP thus defining a new protein-protein interaction domain of SKIP. These data suggest that CHES1 recruits SKIP to repress genes important for tumorigenesis and the response to cancer treatments.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
359
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
119-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16102918-Blotting, Western, pubmed-meshheading:16102918-Cell Cycle Proteins, pubmed-meshheading:16102918-Cell Line, Tumor, pubmed-meshheading:16102918-Gene Expression Regulation, pubmed-meshheading:16102918-HeLa Cells, pubmed-meshheading:16102918-Humans, pubmed-meshheading:16102918-Immunoprecipitation, pubmed-meshheading:16102918-Luciferases, pubmed-meshheading:16102918-Nuclear Proteins, pubmed-meshheading:16102918-Nuclear Receptor Coactivators, pubmed-meshheading:16102918-Plasmids, pubmed-meshheading:16102918-Protein Binding, pubmed-meshheading:16102918-Recombinant Fusion Proteins, pubmed-meshheading:16102918-Repressor Proteins, pubmed-meshheading:16102918-Son of Sevenless Proteins, pubmed-meshheading:16102918-Transcription, Genetic, pubmed-meshheading:16102918-Transcription Factors, pubmed-meshheading:16102918-Transfection, pubmed-meshheading:16102918-Two-Hybrid System Techniques
pubmed:year
2005
pubmed:articleTitle
CHES1/FOXN3 interacts with Ski-interacting protein and acts as a transcriptional repressor.
pubmed:affiliation
Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural