title: Crosstalk between JNK and SUMO signaling pathways: deSUMOylation is protective against H2O2-induced cell injury.
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.
  
  
  RESULTS
  With this study we investigated if SUMOylation participates in the regulation of JNK activation as well as cellular death in a model of H(2)O(2) induced-oxidative stress. Our data show that H(2)O(2) modulates JNK 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(2)O(2), SUMO-1 over-expression increased phosphorylation of JNK and exacerbated cell 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 H(2)O(2) induced death. Importantly, in our model, direct interaction between these proteins can occur.
  
  
  CONCLUSIONS
  Taken together our results show that SUMOylation may significantly contribute to modulation of JNK activation and contribute to cell death in oxidative stress conditions.
authors.affiliation: Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Feligioni
authors.forename: Elisa
authors.initials: E
authors.lastname: Brambilla
authors.forename: Agata
authors.initials: A
authors.lastname: Camassa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sclip
authors.forename: Andrea
authors.initials: A
authors.lastname: Arnaboldi
authors.forename: Federica
authors.initials: F
authors.lastname: Morelli
authors.forename: Xanthi
authors.initials: X
authors.lastname: Antoniou
authors.forename: Tiziana
authors.initials: T
authors.lastname: Borsello
mesh_terms: D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D010957:Plasmids / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D025841:Small Ubiquitin-Related Modifier Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; C022616:thiazolyl blue