crosstalk between jnk and sumo signaling pathways desumoylation is protective against h2o2-induced cell injury物之间的串扰和相扑信号通路desumoylation预防h2o2-induced细胞损伤.pdfVIP

Crosstalk between JNK and SUMO Signaling Pathways: deSUMOylation Is Protective against H O -Induced Cell 2 2 Injury Marco Feligioni, Elisa Brambilla, Agata Camassa, Alessandra Sclip, Andrea Arnaboldi, Federica Morelli, Xanthi Antoniou, Tiziana Borsello* Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy Abstract Background: Oxidative stress is a key feature in the pathogenesis of several neurological disorders. Following oxidative stress stimuli a wide range of pathways are activated and contribute to cellular death. The mechanism that couples c-Jun N- terminal kinase (JNK) signaling, a key pathway in stress conditions, to the small ubiquitin-related modifier (SUMO), an emerging protein in the field, is largely unknown. Methodology/Principal Findings: With this study we investigated if SUMOylation participates in the regulation of JNK activation as well as cellular death in a model of H O induced-oxidative stress. Our data show that H O modulates JNK 2 2 2 2 activation and induces cellular death in neuroblastoma SH-SY5Y cells. Inhibition of JNK’s action with the D-JNKI1 peptide rescued cells from death. Following H O , SUMO-1 over-expression increased phosphorylation of JNK and exacerbated cell 2 2 death, although only in conditions of mild oxidative stress. Furthermore inhibition of SUMOylation, following transfection with SENP1, interfered with JNK activation and rescued cells from H2O2 induced death. Importantly, in our model, direct interaction between