title: ER stress does not cause upregulation and activation of caspase-2 to initiate apoptosis.
abstract: A recent report claimed that endoplasmic reticulum (ER) stress activates the ER trans-membrane receptor IRE1α, leading to increased caspase-2 levels via degradation of microRNAs, and consequently induction of apoptosis. This observation casts caspase-2 into a central role in the apoptosis triggered by ER stress. We have used multiple cell types from caspase-2-deficient mice to test this hypothesis but failed to find significant impact of loss of caspase-2 on ER-stress-induced apoptosis. Moreover, we did not observe increased expression of caspase-2 protein in response to ER stress. Our data strongly argue against a critical role for caspase-2 in ER-stress-induced apoptosis.
authors.affiliation: 1] The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: J J
authors.initials: JJ
authors.lastname: Sandow
authors.affiliation: 1] The Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia [2] Department of Medicine, University of Adelaide, Adelaide, SA 5005, Australia [3] Division of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Dorstyn
authors.affiliation: 1] The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: L A
authors.initials: LA
authors.lastname: O'Reilly
authors.affiliation: 1] The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Tailler
authors.affiliation: 1] The Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia [2] Department of Medicine, University of Adelaide, Adelaide, SA 5005, Australia [3] Division of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.affiliation: 1] The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.affiliation: 1] The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: P G
authors.initials: PG
authors.lastname: Ekert
mesh_terms: D000818:Animals; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060168:Thymocytes / Q000201:enzymology / Q000378:metabolism; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C490360:CASP2 protein, human; C090208:Casp2 protein, mouse; D053143:Caspase 2; D003546:Cysteine Endopeptidases