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Publication : Smac/DIABLO is not released from mitochondria during apoptotic signalling in cells deficient in cytochrome c.

First Author  Hansen TM Year  2006
Journal  Cell Death Differ Volume  13
Issue  7 Pages  1181-90
PubMed ID  16239929 Mgi Jnum  J:126299
Mgi Id  MGI:3760962 Doi  10.1038/sj.cdd.4401795
Citation  Hansen TM, et al. (2006) Smac/DIABLO is not released from mitochondria during apoptotic signalling in cells deficient in cytochrome c. Cell Death Differ 13(7):1181-90
abstractText  We have characterised the apoptotic defects in cells null for cytochrome c (cyt c-/-). Such cells treated with staurosporine (STS) exhibited translocation to the mitochondria and activation of the proapoptotic signalling molecule Bax but failed to release Smac/DIABLO from these organelles, judged by both confocal microscopy and Western blotting. While reference cells expressing cytochrome c released both it and Smac/DIABLO under a variety of conditions of apoptotic induction, we have never observed release of Smac/DIABLO from cyt c-/- cells. We eliminate the possibility that proteasomal degradation of cytosolically localised Smac/DIABLO is responsible for our failure to visualise the protein outside the mitochondria. Our findings indicate an unanticipated nexus between release of cytochrome c and Smac/DIABLO from mitochondria, previously thought to be a more or less synchronised event early in apoptosis. We suggest that the failure of cyt c-/- cells to release Smac/DIABLO after recruitment of Bax to mitochondria represents an extreme manifestation of some inherent difference in the regulation of release of these two proteins from mitochondria.
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