title: The proteasome pathway destabilizes Yersinia outer protein E and represses its antihost cell activities.
abstract: Pathogenic Yersinia spp. neutralize host defense mechanisms by engaging a type III protein secretion system that translocates several Yersinia outer proteins (Yops) into the host cell. Although the modulation of the cellular responses by individual Yops has been intensively studied, little is known about the fate of the translocated Yops inside the cell. In this study, we investigated involvement of the proteasome, the major nonlysosomal proteolytic system in eukaryotic cells, in Yop destabilization and repression. Our data show that inhibition of the proteasome in Yersinia enterocolitica-infected cells selectively stabilized the level of YopE, but not of YopH or YopP. In addition, YopE was found to be modified by ubiquitination. This suggests that the cytotoxin YopE is physiologically subjected to degradation via the ubiquitin-proteasome pathway inside the host cell. Importantly, the increased levels of YopE upon proteasome inhibition were associated with decreased activity of its cellular target Rac. Thus, the GTPase-down-regulating function of YopE is enhanced when the proteasome is inhibited. The stabilization of YopE by proteasome inhibitor treatment furthermore led to aggravation of the cytotoxic YopE effects on the actin cytoskeleton and on host cell morphology. Together, these data show that the host cell proteasome functions to destabilize and inactivate the Yersinia effector protein YopE. This implies the proteasome as integral part of the cellular host immune response against the immunomodulatory activities of a translocated bacterial virulence protein.
authors: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Munich, Germany. k.ruckdeschel@uke.uni-hamburg.de
authors: Klaus
authors: K
authors: Ruckdeschel
authors: Gudrun
authors: G
authors: Pfaffinger
authors: Konrad
authors: K
authors: Trülzsch
authors: Gerhardt
authors: G
authors: Zenner
authors: Kathleen
authors: K
authors: Richter
authors: Jürgen
authors: J
authors: Heesemann
authors: Martin
authors: M
authors: Aepfelbacher