XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation

XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation

Perturbations in autophagy and apoptosis are associated with cancer development. XIAP and cIAP1 are two members of the inhibitors of apoptosis protein family whose expression is elevated in different cancers. Here we report that XIAP and cIAP1 induce autophagy by upregulating the transcription of Be...

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Main Authors: Lin, Fang, Ghislat, Ghita, Luo, Shouqing, Renna, Maurizio, Siddiqi, Farah, Rubinsztein, David C.
Format: Online
Language:English
Published: Oxford University Press 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406300/
id pubmed-4406300
recordtype oai_dc
spelling pubmed-44063002015-04-27 XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation Lin, Fang Ghislat, Ghita Luo, Shouqing Renna, Maurizio Siddiqi, Farah Rubinsztein, David C. Articles Perturbations in autophagy and apoptosis are associated with cancer development. XIAP and cIAP1 are two members of the inhibitors of apoptosis protein family whose expression is elevated in different cancers. Here we report that XIAP and cIAP1 induce autophagy by upregulating the transcription of Beclin 1, an essential autophagy gene. The E3 ubiquitin ligase activity of both proteins activates NFκB signalling, leading to the direct binding of p65 to the promoter of Beclin 1 and to its transcriptional activation. This mechanism may be relevant in cancer cells, since we found increased levels of autophagy in different B-cell lymphoma-derived cell lines where XIAP is overexpressed and pharmacological inhibition of XIAP in these cell lines reduced autophagosome biogenesis. Thus, the chemotherapy resistance associated with XIAP and cIAP1 overexpression observed in several human cancers may be, at least in part, due to the Beclin 1-dependent autophagy activation by IAPs described in this study. In this context, the disruption of this increased autophagy might represent a valuable pharmacological tool to be included in combined anti-neoplastic therapies. Oxford University Press 2015-05-15 2015-02-10 /pmc/articles/PMC4406300/ /pubmed/25669656 http://dx.doi.org/10.1093/hmg/ddv052 Text en © The Author 2015. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Lin, Fang
Ghislat, Ghita
Luo, Shouqing
Renna, Maurizio
Siddiqi, Farah
Rubinsztein, David C.
spellingShingle Lin, Fang
Ghislat, Ghita
Luo, Shouqing
Renna, Maurizio
Siddiqi, Farah
Rubinsztein, David C.
XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation
author_facet Lin, Fang
Ghislat, Ghita
Luo, Shouqing
Renna, Maurizio
Siddiqi, Farah
Rubinsztein, David C.
author_sort Lin, Fang
title XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation
title_short XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation
title_full XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation
title_fullStr XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation
title_full_unstemmed XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation
title_sort xiap and ciap1 amplifications induce beclin 1-dependent autophagy through nfκb activation
description Perturbations in autophagy and apoptosis are associated with cancer development. XIAP and cIAP1 are two members of the inhibitors of apoptosis protein family whose expression is elevated in different cancers. Here we report that XIAP and cIAP1 induce autophagy by upregulating the transcription of Beclin 1, an essential autophagy gene. The E3 ubiquitin ligase activity of both proteins activates NFκB signalling, leading to the direct binding of p65 to the promoter of Beclin 1 and to its transcriptional activation. This mechanism may be relevant in cancer cells, since we found increased levels of autophagy in different B-cell lymphoma-derived cell lines where XIAP is overexpressed and pharmacological inhibition of XIAP in these cell lines reduced autophagosome biogenesis. Thus, the chemotherapy resistance associated with XIAP and cIAP1 overexpression observed in several human cancers may be, at least in part, due to the Beclin 1-dependent autophagy activation by IAPs described in this study. In this context, the disruption of this increased autophagy might represent a valuable pharmacological tool to be included in combined anti-neoplastic therapies.
publisher Oxford University Press
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406300/
_version_ 1613214441397026816

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