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Cytoprotective effect of the small GTPase RhoB expressed upon treatment of fibroblasts with the Ras‐glucosylating Clostridium sordellii lethal toxin
Author(s) -
Huelsenbeck Johannes,
May Martin,
Schulz Florian,
Schelle Ilona,
Ronkitalia,
Hohenegger Martin,
Fritz Gerhard,
Just Ingo,
Gerhard Ralf,
Genth Harald
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.08.024
Subject(s) - rhob , apoptosis , small gtpase , clostridium difficile toxin a , biology , microbiology and biotechnology , farnesyltransferase inhibitor , gtpase , cancer research , chemistry , signal transduction , farnesyltransferase , biochemistry , enzyme , clostridium difficile , prenylation , rhoa , antibiotics
Mono‐glucosylation of (H/K/N)Ras by Clostridium sordellii lethal toxin (TcsL) blocks critical survival signaling pathways, resulting in apoptosis. In this study, TcsL and K‐Ras knock‐down by siRNA are presented to result in expression of the cell death‐regulating small GTPase RhoB. TcsL‐induced RhoB expression is based on transcriptional activation involving p38 alpha MAP kinase. Newly synthesized RhoB protein is rapidly degraded in a proteasome‐ and a caspase‐dependent manner, providing first evidence for caspase‐dependent degradation of a Rho family protein. Although often characterised as a pro‐apoptotic protein, RhoB suppresses caspase‐3 activation in TcsL‐treated fibroblasts. The finding on the cytoprotective activity of RhoB in TcsL‐treated cells re‐enforces the concept that RhoB exhibits cytoprotective rather than pro‐apoptotic activity in a cellular background of inactive Ras.