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- Publisher Website: 10.1038/sj.emboj.7600039
- Scopus: eid_2-s2.0-1542380553
- PMID: 14713951
- WOS: WOS:000188921700021
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Article: Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is cell-type-specific
Title | Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is cell-type-specific |
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Authors | |
Keywords | Apaf-1/Ced-4 Apoptosis E2F1 Myogenesis Retinoblastoma Neurogenesis Caspase-9 |
Issue Date | 2004 |
Citation | EMBO Journal, 2004, v. 23, n. 2, p. 460-472 How to Cite? |
Abstract | Inactivation of the tumor suppressor Rb in the mouse induces cell death, which depends entirely (in lens, CNS) and only partly (PNS, skeletal muscles) on Apaf1/Ced4, an apoptosomal factor thought to be required for processing procaspase-9 following mitochondrial permeabilization. Here, we report that in response to cytotoxic drugs, Apaf1-/- primary myoblasts but not fibroblasts undergo bona fide apoptosis. Cell demise was associated with disruption of mitochondria but not endoplasmic reticulum. Processing of procaspase-9 occurred in Apaf1-/- myoblasts but not fibroblasts, and ablation of Casp9 prevented drug-induced apoptosis in both cell types. Deregulation of the Rb pathway by overexpression of E2F1 also induced caspase-9-dependent, Apaf1-independent apoptosis in myoblasts. Despite its requirement for apoptosis in vitro, mutation in Casp9 abrogated cell death in the nervous system and lens but only partly in skeletal muscles of Rb-deficient embryos. In addition, developmental cell death in fetal liver and PNS was not inhibited in Casp9-/- embryos. Therefore, loss of pRb elicits apoptosome-dependent and apoptosome-independent cell death, and the requirement and coupling of caspase-9 to Apaf1 are both context-dependent. |
Persistent Identifier | http://hdl.handle.net/10722/291692 |
ISSN | 2021 Impact Factor: 14.012 2020 SCImago Journal Rankings: 7.484 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Ho, Andrew T. | - |
dc.contributor.author | Li, Qin H. | - |
dc.contributor.author | Hakem, Razqallah | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Zacksenhaus, Eldad | - |
dc.date.accessioned | 2020-11-17T14:54:54Z | - |
dc.date.available | 2020-11-17T14:54:54Z | - |
dc.date.issued | 2004 | - |
dc.identifier.citation | EMBO Journal, 2004, v. 23, n. 2, p. 460-472 | - |
dc.identifier.issn | 0261-4189 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291692 | - |
dc.description.abstract | Inactivation of the tumor suppressor Rb in the mouse induces cell death, which depends entirely (in lens, CNS) and only partly (PNS, skeletal muscles) on Apaf1/Ced4, an apoptosomal factor thought to be required for processing procaspase-9 following mitochondrial permeabilization. Here, we report that in response to cytotoxic drugs, Apaf1-/- primary myoblasts but not fibroblasts undergo bona fide apoptosis. Cell demise was associated with disruption of mitochondria but not endoplasmic reticulum. Processing of procaspase-9 occurred in Apaf1-/- myoblasts but not fibroblasts, and ablation of Casp9 prevented drug-induced apoptosis in both cell types. Deregulation of the Rb pathway by overexpression of E2F1 also induced caspase-9-dependent, Apaf1-independent apoptosis in myoblasts. Despite its requirement for apoptosis in vitro, mutation in Casp9 abrogated cell death in the nervous system and lens but only partly in skeletal muscles of Rb-deficient embryos. In addition, developmental cell death in fetal liver and PNS was not inhibited in Casp9-/- embryos. Therefore, loss of pRb elicits apoptosome-dependent and apoptosome-independent cell death, and the requirement and coupling of caspase-9 to Apaf1 are both context-dependent. | - |
dc.language | eng | - |
dc.relation.ispartof | EMBO Journal | - |
dc.subject | Apaf-1/Ced-4 | - |
dc.subject | Apoptosis | - |
dc.subject | E2F1 | - |
dc.subject | Myogenesis | - |
dc.subject | Retinoblastoma | - |
dc.subject | Neurogenesis | - |
dc.subject | Caspase-9 | - |
dc.title | Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is cell-type-specific | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1038/sj.emboj.7600039 | - |
dc.identifier.pmid | 14713951 | - |
dc.identifier.pmcid | PMC1271749 | - |
dc.identifier.scopus | eid_2-s2.0-1542380553 | - |
dc.identifier.volume | 23 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 460 | - |
dc.identifier.epage | 472 | - |
dc.identifier.isi | WOS:000188921700021 | - |
dc.identifier.issnl | 0261-4189 | - |