RIP3: a molecular switch for necrosis and inflammation.
TLDR
The current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases is reviewed.Abstract:
The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/ necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases.read more
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Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis.
Kim Newton,Debra L. Dugger,Katherine E. Wickliffe,Neeraj Kapoor,M. Cristina de Almagro,Domagoj Vucic,László G. Kömüves,Ronald E. Ferrando,Dorothy French,Joshua D. Webster,Merone Roose-Girma,Søren Warming,Vishva M. Dixit +12 more
TL;DR: The data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis.
Journal ArticleDOI
CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis
Ting Zhang,Yan Zhang,Mingyao Cui,Li Jin,Yimei Wang,Fengxiang Lv,Yuli Liu,Wen Zheng,Haibao Shang,Jun Zhang,Mao Zhang,Hong-Kun Wu,Jiaojiao Guo,Xiuqin Zhang,Xinli Hu,Chun-Mei Cao,Rui-Ping Xiao +16 more
TL;DR: It is shown that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca2+-calmodulin–dependent protein kinase (CaMKII) rather than through the well-established RIP3 partners RIP1 and MLKL.
Journal ArticleDOI
Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics
Gi Bang Koo,Michael J. Morgan,Da Gyum Lee,Woo-Jung Kim,Jung Ho Yoon,Ja Seung Koo,Seung Il Kim,Soo Jung Kim,Mi Kwon Son,Soon-Sun Hong,Jean M. Mulcahy Levy,Daniel A. Pollyea,Craig T. Jordan,Pearlly S. Yan,David Frankhouser,Deedra Nicolet,Kati Maharry,Guido Marcucci,Kyeong Sook Choi,Hyeseong Cho,Andrew Thorburn,You-Sun Kim +21 more
TL;DR: This work shows that programmed necrosis is activated in response to many chemotherapeutic agents and contributes to chemotherapy-induced cell death, and proposes that RIP3-deficient cancer patients may benefit from receiving hypomethylating agents to induce RIP3 expression prior to treatment with conventional Chemotherapeutics.
Journal ArticleDOI
Die another way – non-apoptotic mechanisms of cell death
TL;DR: Several regulated non-apoptotic forms of cell death including necroptosis, autophagic cell death, pyroptosis and caspase-independent cell death are discussed, outlining what the authors know about their mechanism, potential roles in vivo and define outstanding questions.
Journal ArticleDOI
Innate Immunity and Inflammation in NAFLD/NASH.
TL;DR: New insights are presented into the factors promoting the inflammatory response in NASH including sterile cell death processes resulting from lipotoxicity in hepatocytes as well as into the altered gut-liver axis function, which involves translocation of bacterial products into portal circulation as a result of gut leakiness.
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