To characterize the mechanisms underlying apoptosisinduced by viral infection, transcriptional activation ofgenes encoding members of the ‘BH3-only’ family ofproteins was analysed during the course of virus infection.Among these genes, only NOXA is transcriptionallyactivated by vesicular stomatitis virus (VSV), sendai virus(SV), measles virus, herpes simplex virus, or dsRNA andrequired for efficient apoptosis of cells. Transcriptionalactivation of NOXA by VSV or SV is independent of p53,but requires the presence of interferon regulatory factor 1(IRF-1), IRF-3and cAMP-responsive element bindingprotein (CREB). Binding to and transactivation of theNOXA promoter by each of these transcription factorsis governed by post-translational modification involvingdifferent pathways for each factor. Thus, SV infectionactivates IRF-3and CREB by phosphorylation triggeredby Toll like receptor 3signa lling, and a pathway involvingcalcium-independent phopholipase A2, respectively. Inaddition transactivation induced by IRF-1 during viralinfection correlates with a 10 kDa increase in itsmolecular weight, suggesting a covalent linkage with apreviously unknown regulatory polypeptide.

Single-stranded RNA viruses inactivate the transcriptional activity of p53 but induce NOXA-dependent apoptosis via post-translational modifications of IRF-1, IRF-3 and CREB

PALMIERI, Marta;
2007-01-01

Abstract

To characterize the mechanisms underlying apoptosisinduced by viral infection, transcriptional activation ofgenes encoding members of the ‘BH3-only’ family ofproteins was analysed during the course of virus infection.Among these genes, only NOXA is transcriptionallyactivated by vesicular stomatitis virus (VSV), sendai virus(SV), measles virus, herpes simplex virus, or dsRNA andrequired for efficient apoptosis of cells. Transcriptionalactivation of NOXA by VSV or SV is independent of p53,but requires the presence of interferon regulatory factor 1(IRF-1), IRF-3and cAMP-responsive element bindingprotein (CREB). Binding to and transactivation of theNOXA promoter by each of these transcription factorsis governed by post-translational modification involvingdifferent pathways for each factor. Thus, SV infectionactivates IRF-3and CREB by phosphorylation triggeredby Toll like receptor 3signa lling, and a pathway involvingcalcium-independent phopholipase A2, respectively. Inaddition transactivation induced by IRF-1 during viralinfection correlates with a 10 kDa increase in itsmolecular weight, suggesting a covalent linkage with apreviously unknown regulatory polypeptide.
NOXA; p53; IRF-1; IRF-3; virus
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/308038
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