RGD Reference Report - An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury. - Rat Genome Database

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An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury.

Authors: Luke, CJ  Pak, SC  Askew, YS  Naviglia, TL  Askew, DJ  Nobar, SM  Vetica, AC  Long, OS  Watkins, SC  Stolz, DB  Barstead, RJ  Moulder, GL  Bromme, D  Silverman, GA 
Citation: Luke CJ, etal., Cell. 2007 Sep 21;130(6):1108-19.
RGD ID: 8553611
Pubmed: PMID:17889653   (View Abstract at PubMed)
PMCID: PMC2128786   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2007.07.013   (Journal Full-text)

Extracellular serpins such as antithrombin and alpha1-antitrypsin are the quintessential regulators of proteolytic pathways. In contrast, the biological functions of the intracellular serpins remain obscure. We now report that the C. elegans intracellular serpin, SRP-6, exhibits a prosurvival function by blocking necrosis. Minutes after hypotonic shock, srp-6 null animals underwent a catastrophic series of events culminating in lysosomal disruption, cytoplasmic proteolysis, and death. This newly defined hypo-osmotic stress lethal (Osl) phenotype was dependent upon calpains and lysosomal cysteine peptidases, two in vitro targets of SRP-6. By protecting against both the induction of and the lethal effects from lysosomal injury, SRP-6 also blocked death induced by heat shock, oxidative stress, hypoxia, and cation channel hyperactivity. These findings suggest that multiple noxious stimuli converge upon a peptidase-driven, core stress response pathway that, in the absence of serpin regulation, triggers a lysosomal-dependent necrotic cell death routine.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Capn2Ratprotein binding enablesIPIUniProtKB:G5EFH4PMID:17889653IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Capn2  (calpain 2)


Additional Information