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Article: Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes

TitleEssential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes
Authors
KeywordsCell death
Caspase
MEFs
CPP32
Apoptosis
Issue Date1998
Citation
Genes and Development, 1998, v. 12, n. 6, p. 806-819 How to Cite?
AbstractCaspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3- 1-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of GPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32-/- MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not γ-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFα treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-1-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.
Persistent Identifierhttp://hdl.handle.net/10722/291699
ISSN
2023 Impact Factor: 7.5
2023 SCImago Journal Rankings: 5.015
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWoo, Minna-
dc.contributor.authorHakem, Razqallah-
dc.contributor.authorSoengas, Maria S.-
dc.contributor.authorDuncan, Gordon S.-
dc.contributor.authorShahinian, Arda-
dc.contributor.authorKägi, David-
dc.contributor.authorHakem, Anne-
dc.contributor.authorMcCurrach, Mila-
dc.contributor.authorKhoo, Wilson-
dc.contributor.authorKaufman, Stephen A.-
dc.contributor.authorSenaldi, Giorgio-
dc.contributor.authorHoward, Tamara-
dc.contributor.authorLowe, Scott W.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:54:55Z-
dc.date.available2020-11-17T14:54:55Z-
dc.date.issued1998-
dc.identifier.citationGenes and Development, 1998, v. 12, n. 6, p. 806-819-
dc.identifier.issn0890-9369-
dc.identifier.urihttp://hdl.handle.net/10722/291699-
dc.description.abstractCaspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3- 1-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of GPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32-/- MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not γ-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFα treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-1-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.-
dc.languageeng-
dc.relation.ispartofGenes and Development-
dc.subjectCell death-
dc.subjectCaspase-
dc.subjectMEFs-
dc.subjectCPP32-
dc.subjectApoptosis-
dc.titleEssential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1101/gad.12.6.806-
dc.identifier.pmid9512515-
dc.identifier.pmcidPMC316633-
dc.identifier.scopuseid_2-s2.0-15644364847-
dc.identifier.volume12-
dc.identifier.issue6-
dc.identifier.spage806-
dc.identifier.epage819-
dc.identifier.isiWOS:000072770300006-
dc.identifier.issnl0890-9369-

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