Back to Search
Start Over
A peptide inhibitor of cytochrome c/inositol 1 ,4,5-trisphosph ate receptor binding blocks. intrinsic and extrinsic cell death pathways.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 2/1/2005, Vol. 102 Issue 5, p1466-1471. 6p. - Publication Year :
- 2005
-
Abstract
- Apoptotic stimuli augment intracellular calcium concentration through inositol 1,4,5-trisphosphate receptors (IP3R) on endoplasmic reticulum calcium stores. We previously discovered an apoptotic cascade wherein cytochrome c binds to IP3R early in apoptosis, resulting in dysregulated calcium release Here we show that cytochrome c binding to IP3R depends on a cluster of glutamic acid residues within the C terminus of the channel. A cell permeant peptide derived from this sequence displaces cytochrome c from IP3R and abrogates cell death induced by staurosporine treatment of HeLa cells and Fas ligand stimulation of Jurkat cells. Small-molecule inhibitors of cytochrome c/IP3R interactions may prove useful in treating disorders associated with inappropriate intrinsic and extrinsic apoptotic signaling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 102
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 16301752
- Full Text :
- https://doi.org/10.1073/pnas.0409650102