Oncoprotein suppression of tumor necrosis factor-induced NFκB activation is independent of Raf-controlled pathways

Julie L. Hanson, Vasiliki Anest, Julie Reuther-Madrid, Albert S. Baldwin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Extensive data indicate that the transcription factor NFκB is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region (BCR)ABL. Consistent with this, evidence has been presented that NFκB activity is required for Ras and BCR-ABL to transform cells. However, it remains unclear whether these oncoproteins activate a full spectrum of NFκB-dependent gene expression or whether they may augment or interfere with other stimuli that activate NFκB. The data presented here indicate that BCR-ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor (TNF) to activate NFκB. This suppression of NFκB is manifested by an inhibition of TNF-induced inhibitor of NFκB (IKK) activity and NFκB DNA binding potential but not by blocking TNF-induced nuclear accumulation of NFκB/p65. The inhibition of NFκB is not observed in oncogenic Raf-expressing cells and is not fully restored by the suppression of PI3-kinase or MEK pathways. Oncogenic Ras suppresses the ability of TNF to activate the expression of NFκB-dependent genes, such as iNOS (inducible nitric oxide synthase) and RANTES (regulated on activation normal T-cell expressed and secreted). These studies suggest that the ability of Ras and BCRABL to activate NFκB involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.

Original languageEnglish (US)
Pages (from-to)34910-34917
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
StatePublished - Sep 12 2003

Fingerprint

Oncogene Proteins
Tumor Necrosis Factor-alpha
Chemical activation
Mitogen-Activated Protein Kinase Kinases
T-cells
Nitric Oxide Synthase Type II
Myeloid Cells
Fibroblasts
Phosphatidylinositol 3-Kinases
Gene expression
Transcription Factors
Genes
T-Lymphocytes
Gene Expression
DNA

Cite this

Oncoprotein suppression of tumor necrosis factor-induced NFκB activation is independent of Raf-controlled pathways. / Hanson, Julie L.; Anest, Vasiliki; Reuther-Madrid, Julie; Baldwin, Albert S.

In: Journal of Biological Chemistry, Vol. 278, No. 37, 12.09.2003, p. 34910-34917.

Research output: Contribution to journalArticle

Hanson, Julie L. ; Anest, Vasiliki ; Reuther-Madrid, Julie ; Baldwin, Albert S. / Oncoprotein suppression of tumor necrosis factor-induced NFκB activation is independent of Raf-controlled pathways. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 37. pp. 34910-34917.
@article{4c2bfb8dcc974e749a0691ddfa588a27,
title = "Oncoprotein suppression of tumor necrosis factor-induced NFκB activation is independent of Raf-controlled pathways",
abstract = "Extensive data indicate that the transcription factor NFκB is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region (BCR)ABL. Consistent with this, evidence has been presented that NFκB activity is required for Ras and BCR-ABL to transform cells. However, it remains unclear whether these oncoproteins activate a full spectrum of NFκB-dependent gene expression or whether they may augment or interfere with other stimuli that activate NFκB. The data presented here indicate that BCR-ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor (TNF) to activate NFκB. This suppression of NFκB is manifested by an inhibition of TNF-induced inhibitor of NFκB (IKK) activity and NFκB DNA binding potential but not by blocking TNF-induced nuclear accumulation of NFκB/p65. The inhibition of NFκB is not observed in oncogenic Raf-expressing cells and is not fully restored by the suppression of PI3-kinase or MEK pathways. Oncogenic Ras suppresses the ability of TNF to activate the expression of NFκB-dependent genes, such as iNOS (inducible nitric oxide synthase) and RANTES (regulated on activation normal T-cell expressed and secreted). These studies suggest that the ability of Ras and BCRABL to activate NFκB involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.",
author = "Hanson, {Julie L.} and Vasiliki Anest and Julie Reuther-Madrid and Baldwin, {Albert S.}",
year = "2003",
month = "9",
day = "12",
doi = "10.1074/jbc.M304189200",
language = "English (US)",
volume = "278",
pages = "34910--34917",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "37",

}

TY - JOUR

T1 - Oncoprotein suppression of tumor necrosis factor-induced NFκB activation is independent of Raf-controlled pathways

AU - Hanson, Julie L.

AU - Anest, Vasiliki

AU - Reuther-Madrid, Julie

AU - Baldwin, Albert S.

PY - 2003/9/12

Y1 - 2003/9/12

N2 - Extensive data indicate that the transcription factor NFκB is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region (BCR)ABL. Consistent with this, evidence has been presented that NFκB activity is required for Ras and BCR-ABL to transform cells. However, it remains unclear whether these oncoproteins activate a full spectrum of NFκB-dependent gene expression or whether they may augment or interfere with other stimuli that activate NFκB. The data presented here indicate that BCR-ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor (TNF) to activate NFκB. This suppression of NFκB is manifested by an inhibition of TNF-induced inhibitor of NFκB (IKK) activity and NFκB DNA binding potential but not by blocking TNF-induced nuclear accumulation of NFκB/p65. The inhibition of NFκB is not observed in oncogenic Raf-expressing cells and is not fully restored by the suppression of PI3-kinase or MEK pathways. Oncogenic Ras suppresses the ability of TNF to activate the expression of NFκB-dependent genes, such as iNOS (inducible nitric oxide synthase) and RANTES (regulated on activation normal T-cell expressed and secreted). These studies suggest that the ability of Ras and BCRABL to activate NFκB involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.

AB - Extensive data indicate that the transcription factor NFκB is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region (BCR)ABL. Consistent with this, evidence has been presented that NFκB activity is required for Ras and BCR-ABL to transform cells. However, it remains unclear whether these oncoproteins activate a full spectrum of NFκB-dependent gene expression or whether they may augment or interfere with other stimuli that activate NFκB. The data presented here indicate that BCR-ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor (TNF) to activate NFκB. This suppression of NFκB is manifested by an inhibition of TNF-induced inhibitor of NFκB (IKK) activity and NFκB DNA binding potential but not by blocking TNF-induced nuclear accumulation of NFκB/p65. The inhibition of NFκB is not observed in oncogenic Raf-expressing cells and is not fully restored by the suppression of PI3-kinase or MEK pathways. Oncogenic Ras suppresses the ability of TNF to activate the expression of NFκB-dependent genes, such as iNOS (inducible nitric oxide synthase) and RANTES (regulated on activation normal T-cell expressed and secreted). These studies suggest that the ability of Ras and BCRABL to activate NFκB involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF-induced IKK pathway through a Raf/MEK/Erk-independent mechanism.

UR - http://www.scopus.com/inward/record.url?scp=0042317231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042317231&partnerID=8YFLogxK

U2 - 10.1074/jbc.M304189200

DO - 10.1074/jbc.M304189200

M3 - Article

C2 - 12851413

AN - SCOPUS:0042317231

VL - 278

SP - 34910

EP - 34917

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 37

ER -