A new way to regulate inflammation: selective autophagic degradation of IKKγ mediated by ANGPTL8
Authors:Yu Zhang1, Ling Zheng2 and Kun Huang1
1 Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, P.R.China, 430030.
2 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, P.R.China, 430072.
Keywords:
NF-κB, ANGPTL8, signal transduction, oligomerization, selective autophagy.
Corresponding Author(s):
Conflict of interest statement:
No potential conflicts of interest were disclosed.
Please cite this article as:
Yu Zhang, Ling Zheng and Kun Huang (2018). A new way to regulate inflammation: selective autophagic degradation of IKKγ mediated by ANGPTL8. Cell Stress 2(3): 66-68. doi: 10.15698/cst2018.03.128
© 2018 Zhang et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Transcription factor nuclear factor-κB (NF-κB) plays pivotal roles in the regulation of inflammation and immunity. However, the precise mechanism of NF-κB activation is not fully elucidated. We recently found that Angiopoietin like protein 8 (ANGPTL8, also known as Lipasin, RIFL, TD26 or C19orf80), which is a previously identified secreted metabolic regulator, also can work intracellularly as a negative feedback inhibitor of NF-κB activation. Mechanistically, ANGPTL8 is induced by TNFα stimulation, a classic inducer for NF-κB activation; then, the intracellular ANGPTL8 self-associates via its N-terminal region and interacts with Sequestosome-1 (p62/SQSTM1). The resulting ANGPTL8-p62 aggregates work as a platform in the recruitment and autophagic degradation of IκB kinase gamma (IKKγ/NEMO). Consistently, in patients diagnosed with infectious diseases, enhanced circulating ANGPTL8 levels were detected. These findings suggest a new role for selective autophagy in the regulation of signal transduction and inflammation.