Publication Date:
2015-04-02
Description:
The activation of NF-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 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 modifications in a timely and lesion-specific manner remains unclear. In this study, we demonstrate that LRP16 constitutively interacts with PARP1 and IKK. This interaction is essential for efficient interactions among PARP1, IKK, and PIASy, the modifications of IKK, and the activation of NF-B following DSB induction. The regulation of LRP16 in NF-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, functions to facilitate the lesion-specific recruitment of PARP1 and IKK and, ultimately, the concomitant recruitment of PIASy to IKK in response to DSB damage. Therefore, the study has provided important new mechanistic insights concerning DSB-induced NF-B activation.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
