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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2007-3-22
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pubmed:abstractText |
Mutational activation of BRAF is a frequent event in human malignant melanomas suggesting that BRAF-dependent signaling is conducive to melanoma cell growth and survival. Previously published work reported that melanoma cells exhibit constitutive anti-apoptotic nuclear factor kappaB (NF-kappaB) transcription factor activation triggered by proteolysis of its inhibitor IkappaB. IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. Here, we report that melanocytes expressing a conditionally oncogenic form of BRAF(V600E) exhibit enhanced beta-Trcp expression, increased IKK activity and a concomitant increase in the rate of IkappaBalpha degradation. Conversely, inhibition of BRAF signaling using either a broad-spectrum Raf inhibitor (BAY 43-9006) or by selective knock-down of BRAF(V600E) expression by RNA interference in human melanoma cells leads to decreased IKK activity and beta-Trcp expression, stabilization of IkappaB, inhibition of NF-kappaB transcriptional activity and sensitization of these cells to apoptosis. Taken together, these data support a model in which mutational activation of BRAF in human melanomas contributes to constitutive induction of NF-kappaB activity and to increased survival of melanoma cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-10318790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-10537278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-10758165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-10837071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-11406569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-11850814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-12151397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-12387745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-12591721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-12594806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-14500344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-14678966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-15021890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-15150094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-15781657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-16382039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-16424035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-16452220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-16467110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-16524427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17001349-9346241
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1954-8
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pubmed:dateRevised |
2011-3-18
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pubmed:meshHeading |
pubmed-meshheading:17001349-Cell Line, Tumor,
pubmed-meshheading:17001349-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17001349-Humans,
pubmed-meshheading:17001349-Hydrolysis,
pubmed-meshheading:17001349-Melanoma,
pubmed-meshheading:17001349-NF-kappa B,
pubmed-meshheading:17001349-Phosphorylation,
pubmed-meshheading:17001349-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:17001349-RNA Interference,
pubmed-meshheading:17001349-beta-Transducin Repeat-Containing Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells.
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pubmed:affiliation |
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6046, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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