An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks
The activation of NF-κB has emerged as an important mechanism for the modulation of the response to DNA double-strand breaks (DSBs). The concomitant SUMOylation and phosphorylation of IKKγ by PIASy and ATM, respectively, is a key event in this mechanism. However, the mechanism through which mammalia...
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| Format: | Online |
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Oxford University Press
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381070/ |
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pubmed-43810702015-04-03 An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks Wu, Zhiqiang Wang, Chunmeng Bai, Miaomiao Li, Xiaolei Mei, Qian Li, Xiang Wang, Yao Fu, Xiaobing Luo, Guangbin Han, Weidong Genome Integrity, Repair and Replication The activation of NF-κB has emerged as an important mechanism for the modulation of the response to DNA double-strand breaks (DSBs). The concomitant SUMOylation and phosphorylation of IKKγ by PIASy and ATM, respectively, is a key event in this mechanism. However, the mechanism through which mammalian cells are able to accomplish these IKKγ modifications in a timely and lesion-specific manner remains unclear. In this study, we demonstrate that LRP16 constitutively interacts with PARP1 and IKKγ. This interaction is essential for efficient interactions among PARP1, IKKγ, and PIASy, the modifications of IKKγ, and the activation of NF-κB following DSB induction. The regulation of LRP16 in NF-κB activation is dependent on the DSB-specific sensors Ku70/Ku80. These data strongly suggest that LRP16, through its constitutive interactions with PARP1 and IKKγ, functions to facilitate the lesion-specific recruitment of PARP1 and IKKγ and, ultimately, the concomitant recruitment of PIASy to IKKγ in response to DSB damage. Therefore, the study has provided important new mechanistic insights concerning DSB-induced NF-κB activation. Oxford University Press 2015-03-31 2015-03-03 /pmc/articles/PMC4381070/ /pubmed/25735744 http://dx.doi.org/10.1093/nar/gkv161 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. 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 |
Wu, Zhiqiang Wang, Chunmeng Bai, Miaomiao Li, Xiaolei Mei, Qian Li, Xiang Wang, Yao Fu, Xiaobing Luo, Guangbin Han, Weidong |
| spellingShingle |
Wu, Zhiqiang Wang, Chunmeng Bai, Miaomiao Li, Xiaolei Mei, Qian Li, Xiang Wang, Yao Fu, Xiaobing Luo, Guangbin Han, Weidong An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks |
| author_facet |
Wu, Zhiqiang Wang, Chunmeng Bai, Miaomiao Li, Xiaolei Mei, Qian Li, Xiang Wang, Yao Fu, Xiaobing Luo, Guangbin Han, Weidong |
| author_sort |
Wu, Zhiqiang |
| title |
An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks |
| title_short |
An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks |
| title_full |
An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks |
| title_fullStr |
An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks |
| title_full_unstemmed |
An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks |
| title_sort |
lrp16-containing preassembly complex contributes to nf-κb activation induced by dna double-strand breaks |
| description |
The activation of NF-κB has emerged as an important mechanism for the modulation of the response to DNA double-strand breaks (DSBs). The concomitant SUMOylation and phosphorylation of IKKγ by PIASy and ATM, respectively, is a key event in this mechanism. However, the mechanism through which mammalian cells are able to accomplish these IKKγ modifications in a timely and lesion-specific manner remains unclear. In this study, we demonstrate that LRP16 constitutively interacts with PARP1 and IKKγ. This interaction is essential for efficient interactions among PARP1, IKKγ, and PIASy, the modifications of IKKγ, and the activation of NF-κB following DSB induction. The regulation of LRP16 in NF-κB activation is dependent on the DSB-specific sensors Ku70/Ku80. These data strongly suggest that LRP16, through its constitutive interactions with PARP1 and IKKγ, functions to facilitate the lesion-specific recruitment of PARP1 and IKKγ and, ultimately, the concomitant recruitment of PIASy to IKKγ in response to DSB damage. Therefore, the study has provided important new mechanistic insights concerning DSB-induced NF-κB activation. |
| publisher |
Oxford University Press |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381070/ |
| _version_ |
1613206049910685696 |