Regulation by Rho family GTPases of IL–1 receptor induced signaling: C3-like chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways involved in IL-2 gene expression

Dreikhausen, Ursula; Varga, Georg; Hofmann, Fred; Barth, Holger; Aktories, Klaus; Resch, Klaus; Szamel, Márta

doi:10.1002/1521-4141(200105)31:5<1610::aid-immu1610>3.0.co;2-5

Cited by 17 publications

(9 citation statements)

References 36 publications

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“…This appears to contradict a study described above [41], but that study had used a different NFκB reporter (based on HIV) and was not performed using HeLa. Sulciner et al showed that Rac1 operated downstream of IL-1β to activate NFκB [64], and that Rac1 operated downstream of Ras, consistent with other studies [65–67]. Similar to Rac1, Rac2 is a regulator of IL-1-induced NFκB activation, and this system controls IL-2 gene expression [63].…”

Section: Phosphorylation and Degradation Of Iκbα (Positive Regulationsupporting

confidence: 72%

Rho protein GTPases and their interactions with NFκB: crossroads of inflammation and matrix biology

2014

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The RhoGTPases, with RhoA, Cdc42 and Rac being major members, are a group of key ubiquitous proteins present in all eukaryotic organisms that subserve such important functions as cell migration, adhesion and differentiation. The NFκB (nuclear factor κB) is a family of constitutive and inducible transcription factors that through their diverse target genes, play a major role in processes such as cytokine expression, stress regulation, cell division and transformation. Research over the past decade has uncovered new molecular links between the RhoGTPases and the NFκB pathway, with the RhoGTPases playing a positive or negative regulatory role on NFκB activation depending on the context. The RhoA–NFκB interaction has been shown to be important in cytokine-activated NFκB processes, such as those induced by TNFα (tumour necrosis factor α). On the other hand, Rac is important for activating the NFκB response downstream of integrin activation, such as after phagocytosis. Specific residues of Rac1 are important for triggering NFκB activation, and mutations do obliterate this response. Other upstream triggers of the RhoGTPase–NFκB interactions include the suppressive p120 catenin, with implications for skin inflammation. The networks described here are not only important areas for further research, but are also significant for discovery of targets for translational medicine.

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Section: Phosphorylation and Degradation Of Iκbα (Positive Regulationsupporting

confidence: 72%

Rho protein GTPases and their interactions with NFκB: crossroads of inflammation and matrix biology

2014

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“…From a pathophysiological point of view it is important that C3 was shown to alter for example epithelial and endothelial barrier functions (Nusrat et al 1995;Stamatovic et al 2003), the signaling of immune cells including phagocytosis (Caron and Hall 1998), the production of cytokines (Chen et al 2002;Dreikhausen et al 2001), adhesion (Laudanna et al 1996), de-adhesion , and migration of immune cells (Worthylake et al 2001;Millan and Ridley 2005). A very recent study reported that C3stau-producing S. aureus form transcellular tunnels by inactivation of Rho, so-called macroapertures, which lead to the loss of barrier function in endothelial cells (Boyer et al 2006).…”

Section: The Pathogenetic Role Of C3-like Exoenzymesmentioning

confidence: 99%

C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

Vogelsgesang

Pautsch

Aktories

2006

Naunyn-Schmied Arch Pharmacol

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101

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The family of C3-like exoenzymes comprises seven bacterial ADP-ribosyltransferases of different origin. The common hallmark of these exoenzymes is the selective N-ADP-ribosylation of the low molecular mass GTPbinding proteins RhoA, B, and C and inhibition of signal pathways controlled by Rho GTPases. Therefore, C3-like exoenzymes were applied as pharmacological tools for analyses of cellular functions of Rho protein in numerous studies. Recent structural and functional analyses of C3-like exoenzymes provide detailed information on the molecular mechanisms and functional consequences of ADP-ribosylation catalyzed by these toxins. More recently additional non-enzymatic actions of C3-like ADP-ribosyltransferases have been identified showing that C3 transferases from Clostridium botulinum and Clostridium limosum form a GDI-like complex with the Ras-like low molecular mass GTPase Ral without ADP-ribosylation. These results add novel information on the molecular mode of action(s) of C3-like exoenzymes and are discussed in this review.

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“…Rho GTPases are involved positively in the signal transduction because dominant-negative mutant forms of Rac and Cdc42 inhibit these pathways. Accordingly, the inhibition of Rho family GTPases by C. difficile toxin B also blocks c-Jun N-terminal kinase activation in gentamycin-treated auditory hair cells (13) and interleukin-1-induced activation of c-Jun N-terminal kinase, p38 MAPK, and NFB in murine EL-4 thymoma cells (14). The RhoB GTPase also belongs to the Rho GTPase family and shows an identity to RhoA of 86% at the amino acid level.…”

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confidence: 99%

Clostridium difficile Toxin A Induces Expression of the Stress-induced Early Gene Product RhoB

Gerhard

Tatge

Genth

et al. 2005

Journal of Biological Chemistry

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bot -catalyzed ADP-ribosylation. A pull-down assay in fact revealed a significant amount of active RhoB in toxin A-treated cells that was not present in control cells. We demonstrate for the first time that toxin A has not only the property to inactivate the GTPases RhoA, Rac1, and Cdc42 by glucosylation, but it also has the property to generate active RhoB that likely contributes to the overall picture of toxin treatment.

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Regulation by Rho family GTPases of IL–1 receptor induced signaling: C3-like chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways involved in IL-2 gene expression

Cited by 17 publications

References 36 publications

Rho protein GTPases and their interactions with NFκB: crossroads of inflammation and matrix biology

Rho protein GTPases and their interactions with NFκB: crossroads of inflammation and matrix biology

C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

Clostridium difficile Toxin A Induces Expression of the Stress-induced Early Gene Product RhoB

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