PANZETTA DE DUTARI GRACIELA MARÍA DEL VALLE
Congresos y reuniones científicas
Título:
Staphylococcal -toxin induces activation and degradation of c-JUN and JUND transcription factors
Autor/es:
MOYANO AJ; RACCA AC; ANDREOLI V; SOLA CLAUDIA; GRACIELA M PANZETTA DE DUTARI; BOCCO, JL
Reunión:
Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2012
Institución organizadora:
SAIB
Resumen:
Staphylococcus aureus displays a large set of virulence factors, among which the pore-forming -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 a-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 a-toxindependent
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 a-toxin. These
results shed light on the nuclear response orchestrated by c-Jun and
JunD during cell stress triggered by staphylococcal a-toxin.