@article{2801f1702d9a42dba2dcc6cf1c46dd89,
title = "ABIN-1 regulates RIPK1 activation by linking Met1 ubiquitylation with Lys63 deubiquitylation in TNF-RSC article",
abstract = " Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1. ABIN-1 deficiency reduces the recruitment of A20 and licenses cells to die through necroptosis by promoting Lys63 ubiquitylation and activation of RIPK1 with TNFα stimulation under conditions that would otherwise exclusively activate apoptosis in wild-type cells. Inhibition of RIPK1 kinase and RIPK3 deficiency block the embryonic lethality of Abin-1 -/- mice. We propose that ABIN-1 provides a critical link between Met1 ubiquitylation mediated by the LUBAC complex and Lys63 deubiquitylation by phospho-A20 to modulate the activation of RIPK1.",
author = "Dziedzic, {Slawomir A.} and Zhenyi Su and {Jean Barrett}, Vica and Ayaz Najafov and Mookhtiar, {Adnan K.} and Palak Amin and Heling Pan and Li Sun and Hong Zhu and Averil Ma and Abbott, {Derek W.} and Junying Yuan",
note = "Funding Information: This work was supported in part by grants (to J.Y.) from the NINDS (1R01NS082257) and the NIA (1R01AG047231) and from the Chinese Academy of Sciences, the China Ministry of Science and Technology Program (2014ZX09102001-002), the China National Natural Science Foundation (31530041), the National Key R&D Program of China, and the National Key Research and Development Program (2016YFA0501900). We thank V. Dixit of Genentech for the Ripk3–/– mice and for the antibody against Lys63 ubiquitin chains, M. Pasparakis of University of Cologne, Germany, and M. A. Kelliher of University of Massachusetts, USA, for providing the Ripk1D138N mice, and H. Walczak of Imperial College, UK, for providing the Hoip–/– MEFs. We thank G. Kasof of Cell Signaling for generating the p-Ser166 antibodyand R. Bronson for mouse histopathology analysis. We thank D. Ofengeim and A. D. Yu for comments on the manuscript and the members of the Yuan laboratory for stimulating discussions. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2018",
month = jan,
day = "1",
doi = "10.1038/s41556-017-0003-1",
language = "English (US)",
volume = "20",
pages = "58--68",
journal = "Nature cell biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "1",
}