Lysine and Polyamines Are Substrates for Transglutamination of Rho by the
            <i>Bordetella</i>
            Dermonecrotic Toxin

Schmidt, Gudula; Goehring, Udo-Michael; Schirmer, Joerg; Uttenweiler-Joseph, Sandrine; Wilm, Matthias; Lohmann, Mark; Giese, Arnd; Schmalzing, Guenther; Aktories, Klaus

doi:10.1128/iai.69.12.7663-7670.2001

Cited by 21 publications

(16 citation statements)

References 23 publications

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“…The transamidation by DNT with polyamines such as putrescine or spermine (9,16) occurs at the same amino acid (Gln-63 of RhoA) as deamidation by CNF1. To get further insights into the requirements for Rac degradation concerning effector binding, we studied the activation and degradation of DNT-transamidated Rac by analyzing the fate of DNT-modified cellular Rac with time.…”

Section: Resultsmentioning

confidence: 99%

Isotype-specific Degradation of Rac Activated by the Cytotoxic Necrotizing Factor 1

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Aktories

Schmidt

2004

Journal of Biological Chemistry

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The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli activates members of the Rho family by deamidation of glutamine 61/63. Because this amino acid is crucial for GTP hydrolysis, deamidation of glutamine 61/63 results in constitutively active Rho proteins. Recently, it was shown that the level of CNF1-activated Rac is rapidly diminished in CNF1-treated cells by proteolytic degradation. Here, we studied the requirements for CNF1-induced Rac degradation. By overexpressing His-tagged activated Rac mutants we show that constitutive activation is necessary for degradation of Rac. However, permanent activation is not sufficient for degradation, because Rac that is constitutively activated by transamidation at glutamine 61 by the Bordetella dermonecrotic toxin is not degraded. Overexpression of His-tagged Rac mutants deficient in interaction with GTPase-activating protein (Rac(N92D) and Rac(Y64H)) and guanosine nucleotide dissociation inhibitor (Rac(H103E)) were degraded after activation by CNF1, whereas Rac(Y40C), which is not able to interact with CRIB domain effectors or plenty of SH3, was not degraded. Isoprenylation and the presence of a putative mitotic destruction box are essential for CNF-induced degradation. In contrast to Rac1, Rac2, and Rac3 were not degraded following constitutive activation by CNF1. Using site-directed mutagenesis, we defined the polybasic region and amino acids 90, 107, 147, and 151 as responsible for isotype-specific degradation.

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Section: Resultsmentioning

confidence: 99%

Isotype-specific Degradation of Rac Activated by the Cytotoxic Necrotizing Factor 1

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Aktories

Schmidt

2004

Journal of Biological Chemistry

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“…The RhoAdeamidase domain also possesses transglutaminase activity and can incorporate alkylamines into RhoA at the Gln-63 position [253]. This activity involves two essential C-terminal residues, Cys-866 and His-881 [254].…”

Section: Comparison With Dnt and Cnfmentioning

confidence: 99%

Pasteurella multocida toxin

Wilson

Bergmann

et al. 2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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“…2) ). Recently, putrescine, spermidine and spermine have been identified as in vivo substrates for the transglutamination (Masuda et al 2000;Schmidt et al 2001). At least in vitro, lysine is a preferred substrate for transglutamination by DNT (Schmidt et al 2001).…”

Section: Mode Of Action Of Rho-activating Toxinsmentioning

confidence: 99%

CNF and DNT

Hoffmann

Schmidt

Reviews of Physiology, Biochemistry and Pharmacology

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The actin cytoskeleton of mammalian cells is involved in many processes that affect the growth and colonization of bacteria, such as migration of immune cells, phagocytosis by macrophages, secretion of cytokines, maintenance of epithelial barrier functions and others. With respect to these functions, it is not surprising that many bacterial protein toxins, which are important virulence factors and causative agents of human and/or animal diseases, target the actin cytoskeleton of the host. Some toxins target actin directly, such as the C2 toxin produced by Clostridium botulinum. Moreover, bacterial toxins target the cytoskeleton indirectly by modifying actin regulators such as the low-molecular-mass guanosine triphosphate (GTP)-binding proteins of the Rho family. Remarkably, toxins affect these GTPases in a bidirectional manner. Some toxins inhibit and some activate the GTPases. Here we review the Rho-activating toxins CNF1 and CNF2 (cytotoxic necrotizing factors) from Escherichia coli, the Yersinia CNF(Y) and the dermonecrotic toxin (DNT) from Bordetella species. We describe and compare their uptake into mammalian cells, mode of action, structure-function relationship, substrate specificity and role in diseases.

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Lysine and Polyamines Are Substrates for Transglutamination of Rho by the Bordetella Dermonecrotic Toxin

Cited by 21 publications

References 23 publications

Isotype-specific Degradation of Rac Activated by the Cytotoxic Necrotizing Factor 1

Isotype-specific Degradation of Rac Activated by the Cytotoxic Necrotizing Factor 1

Pasteurella multocida toxin

CNF and DNT

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