| Literature DB >> 30361383 |
Pontus Orning1,2, Dan Weng1,3, Kristian Starheim1,2, Dmitry Ratner1, Zachary Best1, Bettina Lee4, Alexandria Brooks1, Shiyu Xia5, Hao Wu5, Michelle A Kelliher6, Scott B Berger7, Peter J Gough7, John Bertin7, Megan M Proulx8, Jon D Goguen8, Nobuhiko Kayagaki4, Katherine A Fitzgerald1,2, Egil Lien9,2.
Abstract
Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8-dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome-dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.Entities:
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Year: 2018 PMID： 30361383 PMCID： PMC6522129 DOI： 10.1126/science.aau2818
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728