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BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts
- Publication Year :
- 2012
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2012.
-
Abstract
- The proapoptotic activity of BID seems to solely depend upon its cleavage to truncated tBID. Here we demonstrate that expression of a caspase-8 non-cleavable (nc) BID-D59A mutant or expression of wild type (wt) BID induces apoptosis in Bid -/-, caspase-8 -/-, and wt primary MEFs. Western blot analysis indicated that no cleavage products appeared in cells expressing ncBID. ncBID was as effective as wtBID in inducing cytochrome c release, caspase activation, and apoptosis. ncBID and wtBID (nc/wtBID) were much less effective than tBID in localizing to mitochondria and in inducing cytochrome c release, but only slightly less effective in inducing apoptosis. Studies with Apaf-1- and caspase-9-deficient primary MEFs indicated that both proteins were essential for nc/wtBID and for tBID-induced apoptosis. Most importantly, expression of non-apoptotic levels of either ncBID or wtBID in Bid -/- MEFs induced a similar and significant enhancement in apoptosis in response to a variety of death signals, which was accompanied by enhanced localization of BID to mitochondria and cytochrome c release. Thus, these results implicate full-length BID as an active player in the mitochondria during apoptosis.
- Subjects :
- Apoptosis
Cytochrome c Group
Caspase 3
Simian virus 40
Bioinformatics
Caspase 8
Biochemistry
Mice
Western blot
medicine
Animals
APAF1
Molecular Biology
Cells, Cultured
Caspase-9
medicine.diagnostic_test
biology
Chemistry
Cytochrome c
Wild type
Proteins
Cell Biology
Caspase 9
Mitochondria
Cell biology
Apoptotic Protease-Activating Factor 1
Caspases
Mutation
biology.protein
Additions and Corrections
Carrier Proteins
BH3 Interacting Domain Death Agonist Protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....396d23faa1f0ba7f298e08eb0e415542