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

Erscheinungsjahr:

2003

Erschienen:

2003

Enthalten in:

Zur Gesamtaufnahme - volume:278

Enthalten in:

The Journal of biological chemistry - 278(2003), 32 vom: 08. Aug., Seite 29571-80

Sprache:

Englisch

Beteiligte Personen:

Belmokhtar, Chafké Ahmed [VerfasserIn]
Hillion, Josette [VerfasserIn]
Dudognon, Charles [VerfasserIn]
Fiorentino, Susana [VerfasserIn]
Flexor, Maria [VerfasserIn]
Lanotte, Michel [VerfasserIn]
Ségal-Bendirdjian, Evelyne [VerfasserIn]

Themen:

Apaf1 protein, mouse
Apoptotic Protease-Activating Factor 1
Casp3 protein, mouse
Casp9 protein, mouse
Caspase 3
Caspase 9
Caspases
Cytochrome c Group
EC 3.4.21.-
EC 3.4.22.-
Granzymes
Gzmb protein, mouse
H88EPA0A3N
Journal Article
Proteins
RNA, Messenger
Research Support, Non-U.S. Gov't
Serine Endopeptidases
Staurosporine

Anmerkungen:

Date Completed 24.09.2003

Date Revised 09.02.2021

published: Print-Electronic

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM125394683