کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1984769 1539959 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Expression of pokeweed antiviral protein in mammalian cells activates c-Jun NH2-terminal kinase without causing apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Expression of pokeweed antiviral protein in mammalian cells activates c-Jun NH2-terminal kinase without causing apoptosis
چکیده انگلیسی

Pokeweed antiviral protein (PAP) is a ribosome inactivating protein isolated from the pokeweed plant (Phytolacca americana L.) that exhibits broad range antiviral activity against several human viruses including HIV and influenza. This characteristic suggests that PAP may have therapeutic applications; however, it is not known whether the protein elicits a ribotoxic stress response that would result in cell death. Therefore, we expressed PAP in 293T cells and showed that the enzyme did not inhibit protein translation even though approximately 15% of the ribosomal RNA (rRNA) was depurinated. PAP expression induced the activation of c-Jun NH2-terminal kinase (JNK), which was specific to rRNA depurination, as the enzymatically inactive mutant PAPx did not affect kinase activity. Moreover, incubation of PAP-expressing cells with translation inhibitors diminished JNK activation, indicating that the signal for induction of the kinase pathway originated from ribosomes. JNK activation did not result in apoptosis as demonstrated by the absence of caspase-3 and poly(ADP-ribose) polymerase cleavage and by the lack of cell staining for morphological changes in membrane permeability. Unlike all ribosome inactivating proteins tested thus far, the stress response triggered by PAP expression did not result in cell death, which supports further investigation of the enzyme in the design of novel antiviral agents.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 40, Issue 11, 2008, Pages 2452–2461
نویسندگان
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