Staphylococcal alfa toxin regulates c-JUN oncoprotein activation, its mRNA level and protein stability.

SORIA GR; PANZETTA DE DUTARI GM; RACCA AC; SMANIA AM; BOCCO JL ; MOYANO AJ; ANDREOLI V; SOLA C

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2016

c-Jun is a relevant member of the AP-1 transcription complex which participates in a wide range of cellular processes such asproliferation, apoptosis, tumorigenesis, differentiation and survival upon cell stress. However, its role in the context of bacterialinfections has not been thoroughly investigated. Staphylococcus aureus is a worldwide health-care concern pathogen which owns anextensive repertory of virulence factors provoking cellular damage. In this sense, we analyzed the role of staphylococcal α-toxin in theactivation, expression and protein levels of c-Jun in A549 lung epithelial cells. Staphylococcal α-toxin per se was able to activate c-Junby 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 120min. 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 ofthe first steps to understand the role of c-Jun in the cellular response to bacterial pore-forming toxins, placing it as a novel componentof the complex early machinery to face staphylococcal infections.