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

作者：Wu, Zhiqiang; Wang, Chunmeng; Bai, Miaomiao; Li, Xiaolei; Mei, Qian; Li, Xiang; Wang, Yao; Fu, Xiaobing; Luo, Guangbin; Han, Weidong^*

来源：Nucleic Acids Research, 2015, 43(6): 3167-3179.

DOI：10.1093/nar/gkv161

• ESTROGEN-RECEPTOR-ALPHA
• ATM PROTEIN-KINASE
• GENOTOXIC STRESS
• V(D)J RECOMBINATION
• IONIZING-RADIATION
• DAMAGE RESPONSE
• POLY(ADP-RIBOSE)
• PHOSPHORYLATION
• CHROMATIN
• REPAIR

The activation of NF-kappa B has emerged as an important mechanism for the modulation of the response to DNA double-strand breaks (DSBs). The concomitant SUMOylation and phosphorylation of IKK gamma by PIASy and ATM, respectively, is a key event in this mechanism. However, the mechanism through which mammalian cells are able to accomplish these IKK gamma modifications in a timely and lesion-specific manner remains unclear. In this study, we demonstrate that LRP16 constitutively interacts with PARP1 and IKK gamma. This interaction is essential for efficient interactions among PARP1, IKK gamma, and PIASy, the modifications of IKK gamma, and the activation of NF-kappa B following DSB induction. The regulation of LRP16 in NF-kappa B activation is dependent on the DSB-specific sensors Ku70/Ku80. These data strongly suggest that LRP16, through its constitutive interactions with PARP1 and IKK gamma, functions to facilitate the lesion-specific recruitment of PARP1 and IKK gamma and, ultimately, the concomitant recruitment of PIASy to IKK gamma in response to DSB damage. Therefore, the study has provided important new mechanistic insights concerning DSB-induced NF-kappa B activation.

• 出版日期2015-3-31
• 单位中国人民解放军总医院