| uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma. | |
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MedLine Citation:
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PMID: 21964739 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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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Authors:
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Rama Rao Malla; Sreelatha Gopinath; Christopher S Gondi; Kiranmai Alapati; Dzung H Dinh; Andrew J Tsung; Jasti S Rao |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-2 |
Journal Detail:
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Title: Journal of neuro-oncology Volume: - ISSN: 1573-7373 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309335 Medline TA: J Neurooncol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL, 61605, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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