An LRP16-containing preassembly complex contributes to NF-κB activation induced by DNA double-strand breaks

Nucleic Acids Research
Zhiqiang WuWeidong Han

Abstract

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.

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Citations

May 12, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lijuan ShaoKexing Fan
Jan 1, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yu Gang LiuYuan Zhuang
Apr 18, 2019·Open Biology·Luca PalazzoIvan Ahel
Feb 8, 2020·Genes & Development·Johannes Gregor Matthias RackIvan Ahel
Feb 14, 2021·Cells·Kerryanne CrawfordIvan Ahel

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Methods Mentioned

BETA
Transfection
Assay
PCR
Co-IP
immunoprecipitation
electrophoresis
pull-down
fluorescence-activated cell sorting

Software Mentioned

SPSS
ImageJ

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