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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2011-9-21
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pubmed:abstractText |
Jab1, a co-activator of AP-1 transcription factor and the fifth subunit of the COP9 signalosome, mediates degradation of the tumor suppressor p53 and p27(Kip1) and functions as a tumor promoter in different types of human cancer. In this study, we show that inhibition of Bcr-Abl oncogene by imatinib induces down-regulation of Jab1 in Bcr-Abl-positive K562, Ku812, and MEG01 leukemia cells suggesting Bcr-Abl may regulate Jab1 expression. Promoter deletion and mutation analysis indicate the Tcf-4/?-catenin and STAT1 binding sites located between the -405/-223 region of the human Jab1 promoter are important for the activation of Jab1 by Bcr-Abl. Double mutation of these two sites reverses the inhibitory effect of imatinib. Chromatin immunoprecipitation assay verifies the binding of ?-catenin and STAT1 to human Jab1 promoter. Ectopic expression of dominant-negative Tcf-4 mutant significantly attenuates Jab1 expression while over-expression of ?-catenin and STAT1 cooperatively up-regulates Jab1 promoter activity and mRNA expression. Our results also demonstrate that the AKT signaling pathway is involved in the regulation of Jab1 by Bcr-Abl because the AKT inhibitor LY294002 but not the ERK inhibitor PD98059 reduces Jab1 promoter activity and mRNA expression. Taken together, our results suggest that Bcr-Abl stimulates Jab1 expression via the cooperative interaction of ?-catenin and STAT1 in leukemia cells.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/COPS5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-akt,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TCF4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1097-4652
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
226
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2849-56
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pubmed:meshHeading |
pubmed-meshheading:21935931-Antineoplastic Agents,
pubmed-meshheading:21935931-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:21935931-Cell Line, Tumor,
pubmed-meshheading:21935931-Chromones,
pubmed-meshheading:21935931-Down-Regulation,
pubmed-meshheading:21935931-Enzyme Inhibitors,
pubmed-meshheading:21935931-Flavonoids,
pubmed-meshheading:21935931-Fusion Proteins, bcr-abl,
pubmed-meshheading:21935931-Humans,
pubmed-meshheading:21935931-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21935931-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:21935931-Morpholines,
pubmed-meshheading:21935931-Oncogene Protein v-akt,
pubmed-meshheading:21935931-Peptide Hydrolases,
pubmed-meshheading:21935931-Piperazines,
pubmed-meshheading:21935931-Promoter Regions, Genetic,
pubmed-meshheading:21935931-Pyrimidines,
pubmed-meshheading:21935931-STAT1 Transcription Factor,
pubmed-meshheading:21935931-Transcription Factors,
pubmed-meshheading:21935931-beta Catenin
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pubmed:year |
2011
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pubmed:articleTitle |
Bcr-Abl oncogene stimulates Jab1 expression via cooperative interaction of ?-catenin and STAT1 in chronic myeloid leukemia cells.
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pubmed:affiliation |
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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