Staphylococcal -toxin induces activation and degradation of c-Jun and JunD transcription factors.

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

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Staphylococcus aureus displays a large set of virulence factors, among which the pore-forming toxin α-toxin has been shown to be crucial in the establishment of severe and often fatal infections such as necrotizing pneumonia. However, its molecular mechanisms are not well understood. In the present study we evaluated the role of c-Jun and JunD, two transcription factors of the AP1 complex which are key regulators of cell fate upon diverse stimuli, including microbial infections. Western blot analysis as well as immunofluorescence studies showed a strong α-toxin-induced phosphorylation of c-Jun and JunD with a concomitant decrease of their protein levels. The use of pharmacological inhibitors showed that this phosphorylation was dependent on the JNK signaling pathway. On the other hand, inhibition of p38 and ERK increased the c-Jun and JunD protein levels. Furthermore, pretreatment with the MG132 proteasome inhibitor showed that this pathway contributed to the α-toxin-dependent degradation of c-Jun and JunD. In addition, Real-Time PCR revealed that c-Jun was also downregulated at transcriptional level. Finally, knockdown of c-Jun by siRNA showed that this protein contributed to the host cell survival against α-toxin. These results shed light on the nuclear response orchestrated by c-Jun and JunD during cell stress triggered by staphylococcal α-toxin.