Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

Stefanie C Huelsenbeck; Dennis Roggenkamp; Martin May; Johannes Huelsenbeck; Cord Herbert Brakebusch; Klemens Rottner; Markus Ladwein; Ingo Just; Gerhard Fritz; Gudula Schmidt; Harald Genth

doi:10.1016/j.biocel.2013.05.020

Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

Stefanie C Huelsenbeck, Dennis Roggenkamp, Martin May, Johannes Huelsenbeck, Cord Herbert Brakebusch, Klemens Rottner, Markus Ladwein, Ingo Just, Gerhard Fritz, Gudula Schmidt, Harald Genth

2 Citations (Scopus)

Abstract

RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediate early gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and genotoxic agents. Clostridial glucosylating toxins have been reported to evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1, which positively regulates the activity of the rhoB promoter and RhoB expression. Conversely, the isomeric cytotoxic necrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails to cause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Upon long term treatment with CNF1, RhoB(-/-) mouse embryonic fibroblasts (MEFs) exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB(+/-) MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1.

Original language	English
Journal	International Journal of Biochemistry & Cell Biology
Volume	45
Issue number	8
Pages (from-to)	1767-75
Number of pages	9
ISSN	1357-2725
DOIs	https://doi.org/10.1016/j.biocel.2013.05.020
Publication status	Published - Aug 2013

Keywords

Animals
Bacterial Toxins
Cell Death
Cell Shape
Cytoprotection
Enzyme Activation
Escherichia coli
Escherichia coli Proteins
Gene Expression Regulation
HT29 Cells
HeLa Cells
Humans
Mice
NIH 3T3 Cells
Polyploidy
Promoter Regions, Genetic
RNA, Messenger
Transcriptional Activation
Yersinia pseudotuberculosis
rac1 GTP-Binding Protein
rhoB GTP-Binding Protein

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10.1016/j.biocel.2013.05.020

Cite this

Huelsenbeck, S. C., Roggenkamp, D., May, M., Huelsenbeck, J., Brakebusch, C. H., Rottner, K., Ladwein, M., Just, I., Fritz, G., Schmidt, G., & Genth, H. (2013). Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1. International Journal of Biochemistry & Cell Biology, 45(8), 1767-75. https://doi.org/10.1016/j.biocel.2013.05.020

Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1. / Huelsenbeck, Stefanie C; Roggenkamp, Dennis; May, Martin et al.
In: International Journal of Biochemistry & Cell Biology, Vol. 45, No. 8, 08.2013, p. 1767-75.

Research output: Contribution to journal › Journal article › Research › peer-review

Huelsenbeck, SC, Roggenkamp, D, May, M, Huelsenbeck, J, Brakebusch, CH, Rottner, K, Ladwein, M, Just, I, Fritz, G, Schmidt, G & Genth, H 2013, 'Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1', International Journal of Biochemistry & Cell Biology, vol. 45, no. 8, pp. 1767-75. https://doi.org/10.1016/j.biocel.2013.05.020

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title = "Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1",

abstract = "RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediate early gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and genotoxic agents. Clostridial glucosylating toxins have been reported to evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1, which positively regulates the activity of the rhoB promoter and RhoB expression. Conversely, the isomeric cytotoxic necrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails to cause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Upon long term treatment with CNF1, RhoB(-/-) mouse embryonic fibroblasts (MEFs) exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB(+/-) MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1.",

keywords = "Animals, Bacterial Toxins, Cell Death, Cell Shape, Cytoprotection, Enzyme Activation, Escherichia coli, Escherichia coli Proteins, Gene Expression Regulation, HT29 Cells, HeLa Cells, Humans, Mice, NIH 3T3 Cells, Polyploidy, Promoter Regions, Genetic, RNA, Messenger, Transcriptional Activation, Yersinia pseudotuberculosis, rac1 GTP-Binding Protein, rhoB GTP-Binding Protein",

author = "Huelsenbeck, {Stefanie C} and Dennis Roggenkamp and Martin May and Johannes Huelsenbeck and Brakebusch, {Cord Herbert} and Klemens Rottner and Markus Ladwein and Ingo Just and Gerhard Fritz and Gudula Schmidt and Harald Genth",

year = "2013",

month = aug,

doi = "10.1016/j.biocel.2013.05.020",

language = "English",

volume = "45",

pages = "1767--75",

journal = "International Journal of Biochemistry & Cell Biology",

issn = "1357-2725",

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TY - JOUR

T1 - Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

AU - Huelsenbeck, Stefanie C

AU - Roggenkamp, Dennis

AU - May, Martin

AU - Huelsenbeck, Johannes

AU - Brakebusch, Cord Herbert

AU - Rottner, Klemens

AU - Ladwein, Markus

AU - Just, Ingo

AU - Fritz, Gerhard

AU - Schmidt, Gudula

AU - Genth, Harald

PY - 2013/8

Y1 - 2013/8

N2 - RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediate early gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and genotoxic agents. Clostridial glucosylating toxins have been reported to evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1, which positively regulates the activity of the rhoB promoter and RhoB expression. Conversely, the isomeric cytotoxic necrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails to cause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Upon long term treatment with CNF1, RhoB(-/-) mouse embryonic fibroblasts (MEFs) exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB(+/-) MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1.

AB - RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediate early gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and genotoxic agents. Clostridial glucosylating toxins have been reported to evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1, which positively regulates the activity of the rhoB promoter and RhoB expression. Conversely, the isomeric cytotoxic necrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails to cause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Upon long term treatment with CNF1, RhoB(-/-) mouse embryonic fibroblasts (MEFs) exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB(+/-) MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1.

KW - Animals

KW - Bacterial Toxins

KW - Cell Death

KW - Cell Shape

KW - Cytoprotection

KW - Enzyme Activation

KW - Escherichia coli

KW - Escherichia coli Proteins

KW - Gene Expression Regulation

KW - HT29 Cells

KW - HeLa Cells

KW - Humans

KW - Mice

KW - NIH 3T3 Cells

KW - Polyploidy

KW - Promoter Regions, Genetic

KW - RNA, Messenger

KW - Transcriptional Activation

KW - Yersinia pseudotuberculosis

KW - rac1 GTP-Binding Protein

KW - rhoB GTP-Binding Protein

U2 - 10.1016/j.biocel.2013.05.020

DO - 10.1016/j.biocel.2013.05.020

M3 - Journal article

C2 - 23732113

SN - 1357-2725

VL - 45

SP - 1767

EP - 1775

JO - International Journal of Biochemistry & Cell Biology

JF - International Journal of Biochemistry & Cell Biology

IS - 8

ER -

Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

Abstract

Keywords

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