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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
2007-11-20
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pubmed:abstractText |
Colon cancer is the second leading cause of cancer death in the United States. Krüppel-like factor 4 (KLF4) is a transcription factor involved in both proliferation and differentiation in the colon. It is down-regulated in both mouse and human colonic adenomas and has been implicated as a tumor suppressor in the gut, whereas in breast cancer, KLF4 is an oncogene. KLF4 is also involved in reprogramming differentiated cells into pluripotent stem cells. KLF4 can act as a transcriptional activator or repressor, but the underlying mechanisms are poorly understood. We found that p300, a CREB-binding protein-related protein, interacts with KLF4 both in vitro and in vivo and activates transcription. We further made the novel observation that endogenous KLF4 is acetylated by p300/CBP in vivo and that mutations of the acetylated lysines resulted in a decreased ability of KLF4 to activate target genes, suggesting that acetylation is important for KLF4-mediated transactivation. Furthermore, we found that KLF4 differentially modulates histone H4 acetylation at the promoters of target genes. Co-transfection of KLF4 and HDAC3 resulted in a synergistic repression of a cyclin B(1) reporter construct. Our results suggest that KLF4 might function as an activator or repressor of transcription depending on whether it interacts with co-activators such as p300 and CREB-binding protein or co-repressors such as HDAC3.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CREB-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B1,
http://linkedlifedata.com/resource/pubmed/chemical/GKLF protein,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/histone deacetylase 3
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33994-4002
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pubmed:dateRevised |
2011-5-6
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pubmed:meshHeading |
pubmed-meshheading:17908689-Acetylation,
pubmed-meshheading:17908689-Adenoma,
pubmed-meshheading:17908689-Animals,
pubmed-meshheading:17908689-Breast Neoplasms,
pubmed-meshheading:17908689-CREB-Binding Protein,
pubmed-meshheading:17908689-Cell Differentiation,
pubmed-meshheading:17908689-Cell Line,
pubmed-meshheading:17908689-Cell Proliferation,
pubmed-meshheading:17908689-Colonic Neoplasms,
pubmed-meshheading:17908689-Cyclin B,
pubmed-meshheading:17908689-Cyclin B1,
pubmed-meshheading:17908689-Female,
pubmed-meshheading:17908689-Histone Deacetylases,
pubmed-meshheading:17908689-Histones,
pubmed-meshheading:17908689-Humans,
pubmed-meshheading:17908689-Kruppel-Like Transcription Factors,
pubmed-meshheading:17908689-Male,
pubmed-meshheading:17908689-Mice,
pubmed-meshheading:17908689-Mutation,
pubmed-meshheading:17908689-Organ Specificity,
pubmed-meshheading:17908689-Promoter Regions, Genetic,
pubmed-meshheading:17908689-Protein Processing, Post-Translational,
pubmed-meshheading:17908689-Repressor Proteins,
pubmed-meshheading:17908689-Trans-Activators,
pubmed-meshheading:17908689-Transcription, Genetic,
pubmed-meshheading:17908689-Transcriptional Activation,
pubmed-meshheading:17908689-Tumor Suppressor Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
Kruppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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