Apoptosome-independent pathway for apoptosis. Biochemical analysis of APAF-1 defects and biological outcomes
Induction and execution of apoptosis programs are generally believed to be mediated through a hierarchy of caspase activation. By using two cellular variants obtained from the L1210 cell line (L1210/S and L1210/0), we have shown previously that staurosporine induces apoptotic cell death through both caspase-dependent and caspase-independent pathways. Both pathways normally coexisted in L1210/S cells, whereas L1210/0 cells lacked the ability to activate caspases despite the confirmed presence of both procaspase-3 and -9. Here we show that this defect in caspase activation is not due to mechanisms such as an absence of cytochrome c release, the expression of non-functional caspases, or the presence of an endogenous inhibitor but results from the loss of apoptosis protease activator protein-1 (APAF-1) expression. This absence of APAF-1 protein results from multiple alterations at both genomic and transcriptional levels. However, although this lack of APAF-1 delays the apoptotic program, it does not hamper its execution. Importantly, in these cells, apoptosis develops not only in an APAF-1-independent way but also in the absence of caspase-3 and -9 activation. Altogether these findings provide evidence that apoptosis may occur through alternative signaling pathways independent of APAF-1 expression and totally dissociated from any caspase processing. Therefore, the L1210/0 variant sub-line provides a valuable tool for the elucidation of these pathways.
Medienart: |
Artikel |
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Erscheinungsjahr: |
2003 |
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Erschienen: |
2003 |
Enthalten in: |
Zur Gesamtaufnahme - volume:278 |
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Enthalten in: |
The Journal of biological chemistry - 278(2003), 32 vom: 08. Aug., Seite 29571-80 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Belmokhtar, Chafké Ahmed [VerfasserIn] |
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Anmerkungen: |
Date Completed 24.09.2003 Date Revised 09.02.2021 published: Print-Electronic Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM125394683 |
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100 | 1 | |a Belmokhtar, Chafké Ahmed |e verfasserin |4 aut | |
245 | 1 | 0 | |a Apoptosome-independent pathway for apoptosis. Biochemical analysis of APAF-1 defects and biological outcomes |
264 | 1 | |c 2003 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
338 | |a Band |b nc |2 rdacarrier | ||
500 | |a Date Completed 24.09.2003 | ||
500 | |a Date Revised 09.02.2021 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Induction and execution of apoptosis programs are generally believed to be mediated through a hierarchy of caspase activation. By using two cellular variants obtained from the L1210 cell line (L1210/S and L1210/0), we have shown previously that staurosporine induces apoptotic cell death through both caspase-dependent and caspase-independent pathways. Both pathways normally coexisted in L1210/S cells, whereas L1210/0 cells lacked the ability to activate caspases despite the confirmed presence of both procaspase-3 and -9. Here we show that this defect in caspase activation is not due to mechanisms such as an absence of cytochrome c release, the expression of non-functional caspases, or the presence of an endogenous inhibitor but results from the loss of apoptosis protease activator protein-1 (APAF-1) expression. This absence of APAF-1 protein results from multiple alterations at both genomic and transcriptional levels. However, although this lack of APAF-1 delays the apoptotic program, it does not hamper its execution. Importantly, in these cells, apoptosis develops not only in an APAF-1-independent way but also in the absence of caspase-3 and -9 activation. Altogether these findings provide evidence that apoptosis may occur through alternative signaling pathways independent of APAF-1 expression and totally dissociated from any caspase processing. Therefore, the L1210/0 variant sub-line provides a valuable tool for the elucidation of these pathways | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Apaf1 protein, mouse |2 NLM | |
650 | 7 | |a Apoptotic Protease-Activating Factor 1 |2 NLM | |
650 | 7 | |a Cytochrome c Group |2 NLM | |
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650 | 7 | |a RNA, Messenger |2 NLM | |
650 | 7 | |a Granzymes |2 NLM | |
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650 | 7 | |a Gzmb protein, mouse |2 NLM | |
650 | 7 | |a EC 3.4.21.- |2 NLM | |
650 | 7 | |a Serine Endopeptidases |2 NLM | |
650 | 7 | |a EC 3.4.21.- |2 NLM | |
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650 | 7 | |a Staurosporine |2 NLM | |
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700 | 1 | |a Hillion, Josette |e verfasserin |4 aut | |
700 | 1 | |a Dudognon, Charles |e verfasserin |4 aut | |
700 | 1 | |a Fiorentino, Susana |e verfasserin |4 aut | |
700 | 1 | |a Flexor, Maria |e verfasserin |4 aut | |
700 | 1 | |a Lanotte, Michel |e verfasserin |4 aut | |
700 | 1 | |a Ségal-Bendirdjian, Evelyne |e verfasserin |4 aut | |
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