Unknown

Dataset Information

0

UPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.


ABSTRACT: Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its interaction with 14-3-3? and increased the interaction of BAD with Bcl-xl. Co-depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD, activation of caspase 3 as well as PARP and cytochrome c and SMAC release. These effects were inhibited by FK506 (10 ?M), a specific inhibitor of calcineurin. Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl-2 inhibitor, HA 14-1 (20 ?g/ml). Altered localization and interaction of calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were downregulated. In conclusion, downregulation of uPAR and cathepsin B induced apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.

SUBMITTER: Malla RR 

PROVIDER: S-EPMC3286222 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.

Malla Rama Rao RR   Gopinath Sreelatha S   Gondi Christopher S CS   Alapati Kiranmai K   Dinh Dzung H DH   Tsung Andrew J AJ   Rao Jasti S JS  

Journal of neuro-oncology 20111002 1


Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochond  ...[more]

Similar Datasets

| S-EPMC2966405 | biostudies-literature
| S-EPMC3183416 | biostudies-literature
| S-EPMC2908539 | biostudies-literature
| S-EPMC7396009 | biostudies-literature
| S-EPMC1224117 | biostudies-other
| S-EPMC3367854 | biostudies-literature
| S-EPMC4355738 | biostudies-other
| S-EPMC4061617 | biostudies-literature
| S-EPMC3096680 | biostudies-literature
| S-EPMC3974829 | biostudies-literature