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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-10-12
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pubmed:abstractText |
IkappaB kinase beta (IKKbeta) is involved in tumor development and progression through activation of the nuclear factor (NF)-kappaB pathway. However, the molecular mechanism that regulates IKKbeta degradation remains largely unknown. Here, we show that a Cullin 3 (CUL3)-based ubiquitin ligase, Kelch-like ECH-associated protein 1 (KEAP1), is responsible for IKKbeta ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKKbeta and to upregulation of NF-kappaB-derived tumor angiogenic factors. A systematic analysis of the CUL3, KEAP1, and RBX1 genomic loci revealed a high percentage of genome loss and missense mutations in human cancers that failed to facilitate IKKbeta degradation. Our results suggest that the dysregulation of KEAP1-mediated IKKbeta ubiquitination may contribute to tumorigenesis.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/CA16672,
http://linkedlifedata.com/resource/pubmed/grant/P01 CA099031,
http://linkedlifedata.com/resource/pubmed/grant/P01 CA099031-05S1,
http://linkedlifedata.com/resource/pubmed/grant/P20 CA101936,
http://linkedlifedata.com/resource/pubmed/grant/P30 CA016672-34,
http://linkedlifedata.com/resource/pubmed/grant/P50 CA083639-100009,
http://linkedlifedata.com/resource/pubmed/grant/P50 CA116199,
http://linkedlifedata.com/resource/pubmed/grant/P50 CA116199-050005,
http://linkedlifedata.com/resource/pubmed/grant/P50 CA83639,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA109311,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA109311-05
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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/CUL3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cullin Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/KEAP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RBX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RELA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-4164
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pubmed:author |
pubmed-author:ChangYa-HuiYH,
pubmed-author:ChenChun-TeCT,
pubmed-author:ChouChao-KaiCK,
pubmed-author:DingQingqingQ,
pubmed-author:HsuMing-ChuanMC,
pubmed-author:HungMien-ChieMC,
pubmed-author:HuoLongfeiL,
pubmed-author:KuoHsu-PingHP,
pubmed-author:LaiChien-ChenCC,
pubmed-author:LeeDung-FangDF,
pubmed-author:LiChia-WeiCW,
pubmed-author:LiLong-YuanLY,
pubmed-author:LiaoTsai-LienTL,
pubmed-author:LinAnn-ChiAC,
pubmed-author:LiuMoM,
pubmed-author:RAYT WTW,
pubmed-author:ShenJiaJ,
pubmed-author:TsaiShih-FengSF,
pubmed-author:XiaWeiyaW
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pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
131-40
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:19818716-Animals,
pubmed-meshheading:19818716-Breast Neoplasms,
pubmed-meshheading:19818716-Carrier Proteins,
pubmed-meshheading:19818716-Cell Line,
pubmed-meshheading:19818716-Cell Line, Tumor,
pubmed-meshheading:19818716-Cullin Proteins,
pubmed-meshheading:19818716-DNA Copy Number Variations,
pubmed-meshheading:19818716-Female,
pubmed-meshheading:19818716-Gene Expression,
pubmed-meshheading:19818716-Humans,
pubmed-meshheading:19818716-I-kappa B Kinase,
pubmed-meshheading:19818716-Interleukin-8,
pubmed-meshheading:19818716-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19818716-Kaplan-Meier Estimate,
pubmed-meshheading:19818716-Mice,
pubmed-meshheading:19818716-Mutation,
pubmed-meshheading:19818716-NF-kappa B,
pubmed-meshheading:19818716-Neoplasms,
pubmed-meshheading:19818716-Neovascularization, Physiologic,
pubmed-meshheading:19818716-Protein Binding,
pubmed-meshheading:19818716-Protein Interaction Domains and Motifs,
pubmed-meshheading:19818716-RNA, Small Interfering,
pubmed-meshheading:19818716-Signal Transduction,
pubmed-meshheading:19818716-Transcription Factor RelA,
pubmed-meshheading:19818716-Transfection,
pubmed-meshheading:19818716-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19818716-Ubiquitination
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pubmed:year |
2009
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pubmed:articleTitle |
KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta.
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pubmed:affiliation |
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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