| c-Jun Regulates the Stability of Anti-Apoptotic ΔNp63 in Amyloid-β-Induced Apoptosis. | |
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MedLine Citation:
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PMID: 22045494 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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p63, the structural and functional homologue of p53, is expressed either as a full-length isoform, containing a transactivation (TA) domain (TAp63), or as a truncated isoform, which lacks TA (ΔNp63). Amyloid-β (Aβ) incubation of neuronal cells results in stress-induced cell death through poorly understood mechanisms. We investigated the role of p63 in Aβ-induced stress. Our results show that Aβ-induced apoptosis of rat PC12 neuronal-like cells and primary cortical neurons was associated with stabilization of pro-apoptotic TAp63 and, most importantly, degradation of anti-apoptotic ΔNp63 through a MAPK- and proteasome-dependent mechanism. This was associated with increased c-Jun, and partially modulated by tauroursodeoxycholic acid. As expected, classic genotoxic insults resulted in c-Jun upregulation and concomitant ΔNp63 reduction. Endogenous and ectopic ΔNp63 expression was also markedly reduced by c-Jun overexpression. Further, Aβ-mediated ΔNp63 degradation occurred in a c-Jun-dependent manner. Downregulation of c-Jun expression by specific c-Jun siRNA abrogated the reduction of ΔNp63 levels following Aβ insult, whereas overexpression of c-Jun led to its degradation. c-Jun significantly decreased ΔNp63 half-life. Together, these findings demonstrate that the abundance of anti-apoptotic ΔNp63 in response to Aβ-induced cell stress is regulated by a c-Jun-dependent mechanism, and highlight the importance of finding novel targets for potential therapeutic intervention. |
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Authors:
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Maria B Fonseca; Ana F Nunes; Cecília M P Rodrigues |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-1 |
Journal Detail:
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Title: Journal of Alzheimer's disease : JAD Volume: - ISSN: 1875-8908 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9814863 Medline TA: J Alzheimers Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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