File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Neuroprotective role of the reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice

TitleNeuroprotective role of the reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice
Authors
Issue Date2004
Citation
Molecular and Cellular Biology, 2004, v. 24, n. 22, p. 9848-9862 How to Cite?
AbstractThe serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been implicated in promoting cell death by binding to inhibitor of apoptosis proteins (IAPs) via its amino-terminal Reaper-related motif, thus inducing caspase activity, and also in mediating caspase-independent death through its own protease activity. We report here the phenotype of mice entirely lacking expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These animals, or cells derived from them, show no evidence of reduced rates of cell death but on the contrary suffer loss of a population of neurons in the striatum, resulting in a neurodegenerative disorder with a parkinsonian phenotype that leads to death of the mice around 30 days after birth. The phenotype of these mice suggests that it is the protease function of this protein and not its IAP binding motif that is critical. This conclusion is reinforced by the finding that simultaneous deletion of the other major IAP binding protein, Smac/DIABLO, does not obviously alter the phenotype of HtrA2/Omi knockout mice or cells derived from them. Mammalian HtrA2/Omi is therefore likely to function in vivo in a manner similar to that of its bacterial homologues DegS and DegP, which are involved in protection against cell stress, and not like the proapoptotic Reaper family proteins in Drosophila melanogaster.
Persistent Identifierhttp://hdl.handle.net/10722/291941
ISSN
2023 Impact Factor: 3.2
2023 SCImago Journal Rankings: 1.452
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMartins, L. Miguel-
dc.contributor.authorMorrison, Alastair-
dc.contributor.authorKlupsch, Kristina-
dc.contributor.authorFedele, Valentina-
dc.contributor.authorMoisoi, Nicoleta-
dc.contributor.authorTeismann, Peter-
dc.contributor.authorAbuin, Alejandro-
dc.contributor.authorGrau, Evelyn-
dc.contributor.authorGeppert, Martin-
dc.contributor.authorLivi, George P.-
dc.contributor.authorCreasy, Caretha L.-
dc.contributor.authorMartin, Alison-
dc.contributor.authorHargreaves, Iain-
dc.contributor.authorHeales, Simon J.-
dc.contributor.authorOkada, Hitoshi-
dc.contributor.authorBrandner, Sebastian-
dc.contributor.authorSchulz, Jörg B.-
dc.contributor.authorMak, Tak-
dc.contributor.authorDownward, Julian-
dc.date.accessioned2020-11-17T14:55:26Z-
dc.date.available2020-11-17T14:55:26Z-
dc.date.issued2004-
dc.identifier.citationMolecular and Cellular Biology, 2004, v. 24, n. 22, p. 9848-9862-
dc.identifier.issn0270-7306-
dc.identifier.urihttp://hdl.handle.net/10722/291941-
dc.description.abstractThe serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been implicated in promoting cell death by binding to inhibitor of apoptosis proteins (IAPs) via its amino-terminal Reaper-related motif, thus inducing caspase activity, and also in mediating caspase-independent death through its own protease activity. We report here the phenotype of mice entirely lacking expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These animals, or cells derived from them, show no evidence of reduced rates of cell death but on the contrary suffer loss of a population of neurons in the striatum, resulting in a neurodegenerative disorder with a parkinsonian phenotype that leads to death of the mice around 30 days after birth. The phenotype of these mice suggests that it is the protease function of this protein and not its IAP binding motif that is critical. This conclusion is reinforced by the finding that simultaneous deletion of the other major IAP binding protein, Smac/DIABLO, does not obviously alter the phenotype of HtrA2/Omi knockout mice or cells derived from them. Mammalian HtrA2/Omi is therefore likely to function in vivo in a manner similar to that of its bacterial homologues DegS and DegP, which are involved in protection against cell stress, and not like the proapoptotic Reaper family proteins in Drosophila melanogaster.-
dc.languageeng-
dc.relation.ispartofMolecular and Cellular Biology-
dc.titleNeuroprotective role of the reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/MCB.24.22.9848-9862.2004-
dc.identifier.pmid15509788-
dc.identifier.pmcidPMC525490-
dc.identifier.scopuseid_2-s2.0-7644230386-
dc.identifier.volume24-
dc.identifier.issue22-
dc.identifier.spage9848-
dc.identifier.epage9862-
dc.identifier.isiWOS:000224823300014-
dc.identifier.f10001017797-
dc.identifier.issnl0270-7306-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats