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01-03-2012 | Laboratory Investigation - Human/Animal Tissue

RETRACTED ARTICLE: uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma

Authors: Rama Rao Malla, Sreelatha Gopinath, Christopher S. Gondi, Kiranmai Alapati, Dzung H. Dinh, Andrew J. Tsung, Jasti S. Rao

Published in: Journal of Neuro-Oncology | Issue 1/2012

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 14-3-3ζ 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 μM), 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 μg/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.

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Title: RETRACTED ARTICLE: uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma
Authors: Rama Rao Malla
Sreelatha Gopinath
Christopher S. Gondi
Kiranmai Alapati
Dzung H. Dinh
Andrew J. Tsung
Jasti S. Rao
Publication date: 01-03-2012
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2012
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-011-0727-x

Keynote webinar | Spotlight on medication adherence

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RETRACTED ARTICLE: uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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