Staphylococcal alpha-toxin induces activation of the c-Jun proto-oncoprotein and modifies its mRNA expression and protein stability.

SORIA G.; PANZETTA-DUTARI G.; MOYANO A.J.; ANDREOLI V.; SOLA C.; RACCA AC; SMANIA A.M.; BOCCO J.L.

Córdoba

Congreso; 52° Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular - SAIB 2016; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

c-Jun is a relevant member of the AP-1 transcription complex which participates in a wide range of cellular processes such as proliferation, apoptosis, tumorigenesis, differentiation and survival upon cell stress. However, its role in the context of bacterial infections has not been thoroughly investigated. Staphylococcus aureus is a worldwide health-care concern pathogen which owns an extensive repertory of virulence factors provoking cellular damage. In this sense, we analyzed the role of staphylococcal α-toxin in the activation, expression and protein levels of c-Jun in A549 lung epithelial cells. Staphylococcal α-toxin per se was able to activate c-Jun by inducing phosphorylation of its Ser73 residue. Silencing of the JNK pathway abrogated most of this activation. On the contrary, silencing of ERK exacerbated this response. Cell exposure to α-toxin induced a marked increase in the c-Jun mRNA expression at 120 min. However, the c-Jun protein levels markedly decreased after the same time period as a consequence of proteasomal degradation. Finally, we established that c-Jun contributed to cell survival when cells were challenged with α-toxin. This study constitutes one of the first steps to understand the role of c-Jun in the cellular response to bacterial pore-forming toxins, placing it as a novel component of the complex early machinery to face staphylococcal infections.