p38 MAPK-mediated activation of NF-κB by the RhoGEF domain of Bcr

Korus, Malgorzata; Mahon, Gwendolyn M.; Cheng, Li; Whitehead, Ian P.

doi:10.1038/sj.onc.1205678

Cited by 62 publications

(61 citation statements)

References 64 publications

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“…It has been previously shown that oncogenes such as Bcr, and Ras also activate NF-κB through phosphorylation of p65 [26,31,32]. Thus, we wondered whether either oncogene activates NF-κB in a RhoB-dependent manner.…”

Section: Rhob-dependent Activation Of Nf-κb By Bcrmentioning

confidence: 95%

“…pAX142-rhoB-189/192A has alanine substitutions at residues 189 and 192 and cannot be palmitoylated. Construction of pAX142-IκB(SS), pAX142-H-ras-61L, pAX142-bcr(491-876) and pAX142-Tsg101 have been described previously [22,23]. pCAG-rock(KD) which encodes the kinase-defective version of ROCK I and pCAG-rock(WT) constructs were provided by S. Narumiya [24].…”

Section: Molecular Constructsmentioning

confidence: 99%

“…pCAG-rock(KD) which encodes the kinase-defective version of ROCK I and pCAG-rock(WT) constructs were provided by S. Narumiya [24]. The reporter constructs utilized in the luciferase-coupled transcriptional assays, have been described previously [22,25].…”

Section: Molecular Constructsmentioning

confidence: 99%

“…In Cos-7 cells, siRNAs were transfected 24 hours after the plasmids using siLentFect reagent according to the manufacturer's instructions (Bio-Rad). Analysis of luciferase and β-galactosidase expression was performed as described previously [22]. β-galactosidase activity was determined using Lumi-Gal substrate (Lumigen) according to the manufacturer's instructions.…”

Section: Transient Expression Reporter Gene Assaysmentioning

confidence: 99%

“…Nuclear extracts from 293T cells were prepared as described previously [26]. γ 32P labeling of NF-κB consensus oligonucleotides and subsequent binding reactions were done using the Gel Shift Assay System (Promega) using the protocols provided by the manufacturer.…”

Section: Electrophoretic Mobility Shift Assaysmentioning

confidence: 99%

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ROCK I-mediated activation of NF-κB by RhoB

Rodrı́guez

Sahay

Olabisi

et al. 2007

Cellular Signalling

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RhoB is a short-lived protein whose expression is increased by a variety of extra-cellular stimuli including UV irradiation, epidermal growth factor (EGF) and transforming growth factor β (TGF-β). Whereas most Rho proteins are modified by the covalent attachment of a geranylgeranyl group, RhoB is unique in that it can exist in either a geranylgeranylated (RhoB-GG) or a farnesylated (RhoB-F) form. Although each form is proposed to have different cellular functions, the signaling events that underlie these differences are poorly understood. Here we show that RhoB can activate NF-κB signaling in multiple cell types. Whereas RhoB-F is a potent activator of NF-κB, much weaker activation is observed for RhoB-GG, RhoA, and RhoC. NF-κB activation by RhoB is not associated with increased nuclear translocation of RelA/p65, but rather, by modification of the RelA/p65 transactivation domain. Activation of NF-κB by RhoB is dependent upon ROCK I but not PRK I. Thus, ROCK I cooperates with RhoB to activate NF-κB, and suppression of ROCK I activity by genetic or pharmacological inhibitors blocks NF-κB activation. Suppression of RhoB activity by dominant-inhibitory mutants, or siRNA, blocks NF-κB activation by Bcr, and TSG101, but not by TNFα or oncogenic Ras. Collectively, these observations suggest the existence of an endosomeassociated pathway for NF-κB activation that is preferentially regulated by the farnesylated form of RhoB.

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Section: Rhob-dependent Activation Of Nf-κb By Bcrmentioning

confidence: 95%

Section: Molecular Constructsmentioning

confidence: 99%

Section: Molecular Constructsmentioning

confidence: 99%

Section: Transient Expression Reporter Gene Assaysmentioning

confidence: 99%

Section: Electrophoretic Mobility Shift Assaysmentioning

confidence: 99%

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ROCK I-mediated activation of NF-κB by RhoB

Rodrı́guez

Sahay

Olabisi

et al. 2007

Cellular Signalling

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Induced stabilization of IκBα can facilitate its re‐synthesis and prevent sequential degradation

Place

Haspeslagh

Giardina

2003

Journal Cellular Physiology

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The transcription factor NF-kappaB is responsible for regulating genes that can profoundly impact cell proliferation, apoptosis, inflammation, and immune responses. The NF-kappaB inhibitor IkappaBalpha is rapidly degraded and then re-synthesized after an NF-kappaB stimulus. We have found that the re-synthesis of IkappaBalpha in a human colon-derived cell line (HT-29) includes the post-translational stabilization of newly synthesized IkappaBalpha. The TNF-alpha-induced stabilization of newly synthesized IkappaBalpha involves the C-terminal PEST region of the protein: N-terminal deletion mutants (lacking the IkappaB kinase phosphorylation sites) were readily stabilized by TNF-alpha, whereas deletion of the C-terminus resulted in a constitutively stable protein. The role of the C-terminus in stabilization was further supported by the finding that fusion of the IkappaBalpha C-terminus to GFP generated a protein that could also be stabilized by TNF-alpha. The p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 prevented stabilization of IkappaBalpha and delayed the re-emergence of IkappaBalpha following TNF-alpha-induced degradation. The IkappaBalpha stabilization pathway could prevent sequential rounds of IkappaBalpha degradation without preventing IkappaBalpha phosphorylation. Analysis of two other cell lines (SW480 and THP-1) revealed similarities and cell-specific differences in the regulation of IkappaBalpha stabilization. We propose that cytokine stabilization of newly synthesized IkappaBalpha in some cell types is a critical homeostatic mechanism that limits inflammatory gene expression.

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