| Autor: |
Parcellier A; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland., Tintignac LA, Zhuravleva E, Cron P, Schenk S, Bozulic L, Hemmings BA |
| Jazyk: |
angličtina |
| Zdroj: |
Cellular signalling [Cell Signal] 2009 Apr; Vol. 21 (4), pp. 639-50. Date of Electronic Publication: 2009 Jan 08. |
| DOI: |
10.1016/j.cellsig.2009.01.016 |
| Abstrakt: |
The Carboxy-Terminal Modulator Protein (CTMP) protein was identified as a PKB inhibitor that binds to its hydrophobic motif. Here, we report mitochondrial localization of endogenous and exogenous CTMP. CTMP exhibits a dual sub-mitochondrial localization as a membrane-bound pool and a free pool of mature CTMP in the inter-membrane space. CTMP is released from the mitochondria into the cytosol early upon apoptosis. CTMP overexpression is associated with an increase in mitochondrial membrane depolarization and caspase-3 and polyADP-ribose polymerase (PARP) cleavage. In contrast, CTMP knock-down results in a marked reduction in the loss of mitochondrial membrane potential as well as a decrease in caspase-3 and PARP activation. Mutant CTMP retained in the mitochondria loses its capacity to sensitize cells to apoptosis. Thus, proper maturation of CTMP is essential for its pro-apoptotic function. Finally, we demonstrate that CTMP delays PKB phosphorylation following cell death induction, suggesting that CTMP regulates apoptosis via inhibition of PKB. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect