Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells.

Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Research Abstract Details 

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Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Abstract Text:

J Liu,K G Suresh Kumar,D Yu,S A Molton,M McMahon,M Herlyn,A Thomas-Tikhonenko,S Y Fuchs,

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.

Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Publishing Authors By Initials

J Liu,KG Suresh Kumar,D Yu,SA Molton,M McMahon,M Herlyn,A Thomas-Tikhonenko,SY Fuchs,

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Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Oncogene

VOLUME: 26

Page Numbers: 1954-8

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 25

MONTH: 09

YEAR: 2006

Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711562

Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Keywords Mesh Terms:

KEYWORDS: beta-Transducin Repeat-Containing Protei

MESH TERMS: genetics

Chemical & Substance for Abstract: Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Information

Substance Name: Proto-Oncogene Proteins B-raf

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells.

AFFILIATION: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6046, USA.

Country: England

AGENCY: United States NCI

GRANT: R01 CA092900-06

ACRONYM: CA

MEDLINETA: Oncogene

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